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ImmunoTX Summit 2017

2018-01-232017-03-142017-02-15
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Day 1 - Monday, February 6, 2017
7:45
Welcome & Opening Remarks by Dr. Satish Medicetty, President, GTCbio
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12:25
Lunch Workshop Sponsored by SQI
12:25
Lunch Workshop Sponsored by SQI
12:25
Lunch Workshop Sponsored by SQI
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12:30
Multiplexing with SQI Diagnostics' Custom Assays or Xplex™ Streptavidin Plates
 
Jaymie  Sawyer
Jaymie Sawyer
Vice President, Research & Development
SQI Diagnostics
About Speaker: ... Read Full Bio 
 
 
Jaymie  Sawyer
Jaymie Sawyer
Vice President, Research & Development
SQI Diagnostics
 
About Speaker:
 
Abstract: ...Read More 

SQI Diagnostics offers a unique multiplexed immunoassay technology. Fully-automated microarray assays are employed to measure anti-drug antibodies and differentiate the isotypes of the response in a single well. In our assays, targets of interest are printed as microarrays in a 96-well format. The array format allows the printing of a drug, its subunits or alternate constructs in a single well. Following incubation with test sample, a reporter cocktail containing multiple secondary antibodies each with a different fluorescent tag is added to each well. The signals are detected and quantitated by a multi-wave length scanner. The ability to combine differentially labeled secondary antibodies (anti-isotype or IgG subclass) in a single test brings a keen advantage to the field of bioanalytics and specifically the immunogenicity testing required for biologics.

The SQI platform has also been employed to develop fluorescent bridging assays and multiplexed sandwich assays for biomarker quantitation and PK/trough levels for co-administered drugs.

With SQI’s Xplex streptavidin plates, researchers can develop their own automated assays to detect and isotype anti-drug antibodies. Using microarray positional printing, SQI covalently attaches streptavidin to an epoxysilane glass surface for improved sensitivity. Detectors can be labeled with up to three fluorescent dyes, compatible with the excitation/emission profile of our scanner.

Assay modules include isotyping, sandwich and bridging assays which can be rapidly configured using the Assay Development Toolkit (ADT) and run on any of the SQI analyzers, then automated to support a high-throughput screening environment.

On the sqidlite system, all fluidics are handled on a fully barcoded and LIS compatible automated platform. Our deck configuration will also enable the pre-incubation of samples, serial dilution for further titration, or the loading of samples in a 96 well plate to simplify checkerboard analysis or reduce sample starting volumes.

Our current assays and platform meet international regulatory requirements for IVD release and fit well within the bounds of recently published EMA and FDA Guidelines on bioanalytical method validation.

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Immunogenicity & Immunotoxicity 2017
Strategic Modulation of Immunogenicity
Bonnie Rup, Bonnie Rup Consulting LLC
1:55
Assessing Antigen Specific Immunity as Biomarkers
 
Matthias Herrath
Matthias von Herrath
Professor, La Jolla Institute for Allergy and Immunology
Vice President & Head, Seattle R&D Center, NovoNordisk
About Speaker: Matthias von Herrath, MD, is Vice president and head for the NovoNordisk Type 1 Diabetes Research Center in Seattle and also professor at La Jolla institute. His works centers around immune therapies for type 1 diabetes including biomarkers to assess... Read Full Bio 
 
 
Matthias Herrath
Matthias von Herrath
Professor, La Jolla Institute for Allergy and Immunology
Vice President & Head, Seattle R&D Center, NovoNordisk
 
About Speaker:

Matthias von Herrath, MD, is Vice president and head for the NovoNordisk Type 1 Diabetes Research Center in Seattle and also professor at La Jolla institute. His works centers around immune therapies for type 1 diabetes including biomarkers to assess human antigenic immune responses. he has been the recipient of the 2008 'Outstanding Scientific Achievement Award' by the ADA, the Langerhans Preis by the German Diabetes association in 2014 and was rated #1 type 1 diabetes researcher by Expertscape in 2014.

 
Abstract: Precise assessment of antigen-specifi...Read More 

Precise assessment of antigen-specific immune responses will be required to then determine, whether specific tolerance has been achieved. In mouse models, there are many examples for this, however, in the human situation, there are fewer, currently mostly restricted to the area of allergic responses, where antigenic tolerization has been successful, at least in part. In my talk we will discuss current strategies and obstacles for establishing biomarkers for antigenic immune responses in humans and their assessment in the clinic. These considerations have important implications for immunogenicity and tolerance induction..

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Immunotherapeutics & Immunomonitoring 2017
Conditioning the Tumor Microenvironment for Immunotherapy
Andrew Zloza, Rutgers Cancer Institute of New Jersey
1:55
Harnessing Anti-Pathogen Immune Responses to Recondition the Tumor Microenvironment
 
Andrew  Zloza
Andrew Zloza
Section Chief of Surgical Oncology Research
Rutgers Cancer Institute of New Jersey
About Speaker: Andrew Zloza, MD, PhD, is the Section Chief of Surgical Oncology Research and a member of the Clinical Investigations and Precision Therapeutics Program at Rutgers Cancer Institute of New Jersey (CINJ). He is also an Assistant Professor in the Depart... Read Full Bio 
 
 
Andrew  Zloza
Andrew Zloza
Section Chief of Surgical Oncology Research
Rutgers Cancer Institute of New Jersey
 
About Speaker:

Andrew Zloza, MD, PhD, is the Section Chief of Surgical Oncology Research and a member of the Clinical Investigations and Precision Therapeutics Program at Rutgers Cancer Institute of New Jersey (CINJ). He is also an Assistant Professor in the Department of Surgery at Rutgers Robert W ood Johnson Medical School and the founding Faculty Director of the Immune Monitoring Core at Rutgers CINJ.

Dr. Zloza’s laboratory focuses on defining the effects of infections (exogenous viral and bacterial, endogenous retroviral, and modified oncolytic) on anti-cancer immune responses. Towards this effort he has successfully developed a double-humanized patient-derived xenograft model that allows for in vivo studies of a patient’s anti-cancer immune response in the context of thatpatient’s intact tumor microenvironment. His long-term goals are to utilize patient infectious disease histories towards discovering new cancer immunotherapies and developing a unified theory of infection, cancer, and autoimmunity.

Dr. Zloza earned his BS in Chemical Engineering at the Illinois Institute of Technology (IIT) as part of the IIT/Rush University Honors Program in Engineering and Medicine, and competed his MD and PhD (Immunology/Microbiology) studies at Rush University Medical Center (Chicago, IL). He further trained as a Ruth L. Kirschstein National Research Service Award (NRSA) postdoctoral fellow in tumor immunology and cancer vaccine design at The University of Chicago. In recognition of his successes as a young investigator, he was awarded the 2015 Chambers-eBioscience Memorial Award by the American Association of Immunologists.

 
Abstract: The inte...Read More 

The interplay between infections and cancer has been the subject of great interest for more than a century, since infections have been implicated in having both positive and negative effects on cancer. A minority of pathogens has been proposed to be cancer-causing (i.e., oncogenic) and a minority of pathogen strains has been shown to be cancer-killing (i.e., oncolytic). Although the majority of pathogens are neither oncogenic nor oncolytic, cancer and infections are amongst the two most common human maladies, and patients with cancer are at increased risk of infections. Thus, these pathogens also likely affect the immune response to cancer. We have, therefore, made the study of the interplay between infections and cancer a major focus of our work.

Recently, we discovered that influenza infection in the lung results in accelerated distal skin melanoma growth and subsequent cancer host death. Further, we discovered that infection in a tissue distant from the tumor (i.e., in an unrelated tissue) leads to the accumulation of anti-tumor CD8+ T killer cells at the site of the infection. This likewise leads to a loss of such cells from the tumor microenvironment, and thus, decreases immune surveillance and control within the tumor. Based on this discovery, we have worked towards understanding how this negative impact of infection on distal cancer can be reversed to instead boost anti-tumor immunity. In this presentation, I will report our most recent discoveries in this field and discuss pre-clinical advances that we have made in designing novel immuno-oncology therapeutics that utilize anti-pathogen immune responses to positively recondition the tumor microenvironment and decrease cancer growth and cancer-related deaths.

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Cytokines & Inflammation 2017
Allergy, Asthma, & COPD: Innate Immunity in Respiratory Diseases
Ali Zarrin, Genentech
1:55
Regulation of IL-4 Production in Group 2 Innate Lymphoid Cells
 
Yasutaka  Motomura
Yasutaka Motomura
Special Postdoctoral Researcher
RIKEN
About Speaker: Yasutaka Motomura, Ph.D., is a postdoctoral researcher at RIKEN IMS. He received his undergraduate degree from Tokyo University of Science and graduate degrees in Imunology from Tokyo Medical and Dental University. Dr. Motomura has been engaged in re... Read Full Bio 
 
 
Yasutaka  Motomura
Yasutaka Motomura
Special Postdoctoral Researcher
RIKEN
 
About Speaker:

Yasutaka Motomura, Ph.D., is a postdoctoral researcher at RIKEN IMS. He received his undergraduate degree from Tokyo University of Science and graduate degrees in Imunology from Tokyo Medical and Dental University. Dr. Motomura has been engaged in research on the molecular mechanisms of type 2 cytokine gene regulation (such as IL-4 and IL-13) in T cells and basophils and has identified lineage-specific Il4 gene expression regulatory mechanisms. He has recently been focused on group 2 innate lymphoid cells (ILC2), a new type of innate lymphocyte founded in 2010. His main interest is to unravel the pathogenic mechanisms of allergic disorders by clarifying the regulation of type 2 cytokine genes in ILC2s.

 
Abstract: Group 2 ...Read More 

Group 2 Innate lymphoid cells (ILC2s), a new type of innate lymphocyte that we originally reported as natural helper cells, regulate type2 immune responses such as immunity against helminth infection and allergic responses. ILC2s rapidly produce large amounts of IL-5 and IL-13, which are hallmark cytokines of Th2 cells prior to the acquired immune response, suggesting that ILC2s are the innate counterpart of Th2 cells. The transcription factor GATA3 was found to be critical for regulating the expression of ll5 and Il13 genes in ILC2s as well as Th2 cells. Therefore, it is believed that common molecular mechanisms regulate cytokine genes in ILC2s and Th2 cells. However, although Th2 cells produce IL-4 as well as IL-5 and IL-13 after TCR stimulation, ILC2s fail to produce IL-4 after stimulation with cytokines such as IL-33, suggesting that there is a unique mechanism to regulate IL-4 production in ILC2s.

Here we show strong enrichment of K4 trimethylation on histone H3 at the Il4 gene locus in naive ILC2s similar to that in differentiated Th2 cells. Further, we identified the physiological condition that induces IL-4 production in ILC2s, which is distinct from that in Th2 cells. Taken together, IL-4 production in ILC2s is regulated by a unique mechanism, and ILC2s may play a role in IL-4-mediated immune responses that are distinct from those in Th2 cells.

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2:20
Future Applications of IL-15 for the Therapy of Cancer
 
Thomas  Waldmann
Thomas Waldmann
NIH Distinguished Investigator, Chief of Lymphoid Malignancies Branch
NCI NIH
About Speaker: Thomas A. Waldmann, M.D. received his M.D. from Harvard Medical School. He joined the NCI in 1956, and has been Chief of Lymphoid Malignancies Branch since 1973. Over his 60-year career he defined the IL-2 receptor subunits, IL-2R beta and IL-2R alph... Read Full Bio 
 
 
Thomas  Waldmann
Thomas Waldmann
NIH Distinguished Investigator, Chief of Lymphoid Malignancies Branch
NCI NIH
 
About Speaker:

Thomas A. Waldmann, M.D. received his M.D. from Harvard Medical School. He joined the NCI in 1956, and has been Chief of Lymphoid Malignancies Branch since 1973. Over his 60-year career he defined the IL-2 receptor subunits, IL-2R beta and IL-2R alpha using the first-ever reported anti-cytokine receptor monoclonal antibody (anti-Tac, daclizumab/Zenapax/Zinbryta). These studies culminated in the definition of the IL-2 receptor as an exceptionally valuable target for therapy of leukemia, lymphoma and multiple sclerosis using the monoclonal antibody he developed. He co-discovered IL-15, elucidated its role in persistence of NK and CD8 memory T-cells, and completed a first in-human trial of IL-15 cytokine subcutaneous and continuous infusions in patients with metastatic malignancy. He introduced blockade of the IL-15/IL-15 receptor and its Jak/STAT signaling pathway for leukemias and autoimmune diseases where gamma-c cytokines including IL-15 play a pathogenic role. His honors include: the Ehrlich Medal, Abbott Laboratories Prize, Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, Milken Family Medical Foundation Distinguished Basic Scientist Award, Artois-Baillet Latour Health Prize, AAI-Dana Foundation Award in Human Immunology Research and election to the National Academy of Sciences, American Academy of Arts and Sciences, Institute of Medicine of the National Academy of Sciences and Royal Society of the Medical Sciences (UK).

 
Abstract: Interleu...Read More 

Interleukin-15 (IL-15) acts through a heterotrimeric receptor involving the specific IL-15R alpha subunit and IL-2/IL-15R beta and ?c subunits shared with IL-2. IL-15 plays a pivotal role in the maintenance of natural killer cells and induction of effector memory T-cells. In rhesus macaques continuous intravenous infusion of E. coli rhIL-15 at 20 µg/kg/day was associated with an 80 to 100-fold increase in number of effector memory CD8 T-cells. IL-15 has proven effective in treatment of a number of murine syngeneic tumor models. Clinical trials involving rhIL-15 given by bolus, subcutaneous or continuous intravenous infusion have been completed in patients with metastatic malignancy. Following termination of 10-day continuous intravenous infusion of IL-15 at 2 mcg/kg there was a 30-fold increase in number of NK cells and an over 200-fold increase in the number of CD56bright NK cells. In translation of this effect of IL-15 on NK cells combination therapy of IL-15 with anticancer monoclonal antibodies has shown augmented antibody-dependent, cell-mediated cytotoxicity action and antitumor efficacy in murine models, an observation being translated into clinical trials. Furthermore, IL-15 is being evaluated in association with anti-CTLA4 and anti-PD1 to relieve immune system checkpoints. Combination therapy of IL-15 with agonistic anti-CD40 was associated with an increase in the number of TRAMP-C2 tumor specific CD8 T-cells and synergistic efficacy in prostate cancer treatment. This observation is being translated into a clinical trial of agonistic anti-CD40 + IL-15. It is hoped that combination therapy involving IL-5 will prove of value in treatment of metastatic malignancy.

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2:45
Synthetic Vaccine Particles (SVP) to Treat Food Allergy and Celiac Disease and to Mitigate the Formation of Anti-Drug Antibodies
 
Kei Kishimoto
Kei Kishimoto
Chief Scientific Officer
Selecta Biosciences
About Speaker: Dr. Kishimoto is the Chief Scientific Officer of Selecta Biosciences, a biotechnology company developing synthetic vaccines b ased on a novel self-assembling nanoparticle technology. Prior to joining Selecta, Dr. Kishimoto was Vice President of Resea... Read Full Bio 
 
 
Kei Kishimoto
Kei Kishimoto
Chief Scientific Officer
Selecta Biosciences
 
About Speaker:

Dr. Kishimoto is the Chief Scientific Officer of Selecta Biosciences, a biotechnology company developing synthetic vaccines b ased on a novel self-assembling nanoparticle technology. Prior to joining Selecta, Dr. Kishimoto was Vice President of Research at Momenta Pharmaceuticals where he led multidisciplinary teams in inflammation, oncology, and cardiovascular disease. Previously he was Senior Director of Inflammation Research at Millennium Pharmaceuticals, where he provid ed the scientific leadership for four programs in clinical development, and an Associate Director of Immunology at Boehringer Ingelheim. Dr. Kishimoto receive d his doctoral degree in Immunology from Harvard University and his post-doctoral training at Stanford University.

 
Abstract: ...Read More 
SVPs are capable of delivering instructions to the immune system to specifically induce and modulate antigen-immune responses. We have recently engineered nanoparticles to present antigen in the context of a tolerogenic signal provided by rapamycin to induce antigen-specific immune tolerance. These self-assembling, biodegradable nanoparticles containing rapamycin are capable of inducing durable antigen-specific tolerance that control adaptive immune responses and withstand multiple immunogenic challenges with antigen. The use of tolerogenic nanoparticles can be applied to prevent the formation of anti-drug antibodies (ADAs) against biologic therapies. The development of ADAs is a common cause for treatment failure and adverse events, such as hypersensitivity reactions, associated with biologic therapies. We have demonstrated immune tolerance induction to a variety of biologic drugs in disease-relevant animal models. Tolerogenic nanoparticle therapy for the prevention of ADAs against pegylated uricase in the treatment of hyperuricemia is currently being evaluated in Phase 2 clinical trials. In addition, by changing the payload of the SVP from rapamycin to a Th1-polarizing adjuvant, such as R848 (a TLR7/8 agonist), the SVP can be adapted to develop antigen-specific experimental therapies for the treatment of food allergies by promoting a switch from an allergic (Th2) response to a Th1 response. We have demonstrated that therapeutic treatment with immune switching SVP protects peanut allergic mice from developing anaphylaxis upon challenge with peanut allergen. Importantly, encapsulation of peanut allergens in SVP enables s.c. administration of allergen to peanut allergic animals without provoking an anaphylactic response. The versatile SVP technology has the potential to be adapted to a variety of applications, from traditional vaccines to novel tolerance-inducing or immune switching therapies.
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Allergy, Asthma, & COPD: Innate Immunity in Respiratory Diseases

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3:10
[Short Oral Presentation from Exemplary Submitted Abstracts]
Ali  Zarrin
Ali Zarrin
Senior Scientist
Genentech
 
Ali  Zarrin
Ali Zarrin
Senior Scientist
Genentech
 
About Speaker:

I finished my Ph.D. in immunology at the University of Toronto and joined Fred Alt’s group at Harvard University to complete my postdoctoral research. I joined the Immunology Discovery group at Genentech in the summer of 2007, thus fulfilling my passion for drug discovery research. I am certainly proud of this decision, as I have been able to extend and diversify my expertise in various autoimmune and inflammatory disease areas, allowing me to gain in-depth knowledge about relevant cellular and molecular pathways.

Poly(I:C)-Dependent Anti-inflammatory IL-37b-SIGIRR Negative Feedback Loop is Defective in Cystic Fibrosis Airway Epithelial Cells
Keiko  Ueno-Shuto
Keiko Ueno-Shuto
Laboratory of Pharmacology
Sojo University Pharmacy School
 
Keiko  Ueno-Shuto
Keiko Ueno-Shuto
Laboratory of Pharmacology
Sojo University Pharmacy School
 
About Speaker:
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Immunogenicity & Immunotoxicity 2017
Molecular Mechanisms of Immunogenicity
Dan Sikkema, Frontage Laboratories
4:05
Engineering the T-cell Response for Effective Immunotherapy of Cancer
 
Michelle Krogsgaard
Michelle Krogsgaard
Associate Professor, Department of Pathology and the Perlmutter Cancer Center
New York School of Medicine
About Speaker: Dr. Michelle Krogsgaard is an Associate Professor at Department of Pathology and Perlmutter Cancer Center at New York School of Medicine. She earned her Ph.D. at the University of Copenhagen in Denmark under the supervision of Drs. Jan Engberg and La... Read Full Bio 
 
 
Michelle Krogsgaard
Michelle Krogsgaard
Associate Professor, Department of Pathology and the Perlmutter Cancer Center
New York School of Medicine
 
About Speaker:

Dr. Michelle Krogsgaard is an Associate Professor at Department of Pathology and Perlmutter Cancer Center at New York School of Medicine. She earned her Ph.D. at the University of Copenhagen in Denmark under the supervision of Drs. Jan Engberg and Lars Fugger, where she employed antibody and receptor engineering to develop novel immunological reagents to investigate molecular mechanisms involved in the pathogenesis of multiple sclerosis (MS). Following her Ph.D, work, Dr. Krogsgaard was a postd octoral fellow at Stanford University, where she worked under the supervision of Dr. Mark M. Davis on understanding basic mechanisms of T-cell activation.

In her current position her laboratory is undertaking the investigation of the fundamental question of how effective T-cell responses are generated against foreign and self-antigens. To this end, the research combines cell biological, biochemical and biophysical approaches to explore mechanisms of T-cell recognition, activation and migration, and T-cell effector functions in animal models of human disease and in primary human tissues.

Dr. Krogsgaard was a Alfred Benzon Fellow, a Pew Scholar in the Biomedical Sciences, an American Cancer Society Research Scholar, a Cancer Research Institute investigator and was selected for the Exceptional, Unconventional, Research Enabling Knowledge Advancement (EUREKA) Innovator Award from the National Institute of Health.

 
Abstract: Adoptive...Read More 

Adoptive immunotherapy with antigen-specific T lymphocytes is a powerful strategy for cancer treatment. However, most tumor antigens are non-reactive “self” proteins, which presents an immunotherapy design challenge. Studies have shown that tumor-specific T cell receptors (TCRs) can be transduced into normal peripheral blood lymphocytes, which persist after transfer in about 30% of patients and effectively destroy tumor cells. Still, recent clinical trial with affinity-enhanced TCRs has resulted in severe effects due to cross reactivity to an unrelated peptide. Thus, the challenge for targeted T cell therapy remains to increase T-cell potency in order to improve clinical responses and ensure on-target specificity by avoiding unwanted cross reactivity. Our recent results suggest a relatively low affinity threshold is necessary for the immune system to avoid self -damage given the close relationship between antitumor activity and autoimmunity. This, in turn, indicates that treatment strategies focusing on TCRs in the intermediate affinity range (KD ~10 μM) or targeting shared tumor antigens would dampen the potential for autoimmunity during adoptive T-cell therapy for the treatment of cancer. This presentation will address this this important clinical problem including careful engineering of tumor-specific TCRs using structural based approaches and manipulation of T-cell signaling pathways to carefully balance tumor-reactivity and autoimmunity.

  • Can higher affinity TCRs render ACT more effective
  • Is there an optimal affinity range that balances effective anti-tumor activity and minimal autoimmunity
  • What are the clinical implications for TCR affinity thresholds
  • What are the future strategies to improve the potential of ACT
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Cytokines & Inflammation 2017
Metabolic Regulation of Immunity and Inflammation
Gianluca Matteoli, KU Leuven
4:05
Development of a Compound to Promote the Phenotypic Switch from Pro-Fibrotic to Resolutive Macrophages to Reverse the Fibrosis in Idiopathic Pulmonary Fibrosis
 
Brigitte  Gomperts
Brigitte Gomperts
Associate Professor
UCLA Broad Stem Cell Center
About Speaker: Dr. Gomperts is a physician-scientist who has been a faculty member at UCLA for 14 years. She is an Associate Professor of Pediatrics and Pulmonary Medicine and Co-Director of the Jonsson Comprehensive Cancer Center Cancer Stem Cell Biology Program a... Read Full Bio 
 
 
Brigitte  Gomperts
Brigitte Gomperts
Associate Professor
UCLA Broad Stem Cell Center
 
About Speaker:

Dr. Gomperts is a physician-scientist who has been a faculty member at UCLA for 14 years. She is an Associate Professor of Pediatrics and Pulmonary Medicine and Co-Director of the Jonsson Comprehensive Cancer Center Cancer Stem Cell Biology Program and Vice Chief of Research for Pediatric Hematology-Oncology. Her lab studies repair and regeneration of the lungs, and how the normal repair mechanisms are altered in lung diseases. She is particularly interested in stem/progenitor cell populations in the lungs and determining the regeneration potential of each of these subpopulations in order to better understand repair and the possibility of cell based therapies for lung diseases. Her lab is using novel models to understand repair and regeneration in the proximal and distal lung and has expertise in mouse models of lung diseases and induced pluripotent stem cell lung disease modeling. Major areas of interest include lung fibrosis, mucociliary clearance, Chronic Obstructive Pulmonary Disease and premalignant lesions in the airway. As a physician-scientist, her lab is particularly interested in translational research that will result in new therapies for lung diseases.

 
Abstract: Idiopath...Read More 

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and invariably lethal scarring lung disease that results in tissue remodeling resulting in an inability to breathe. IPF represents the most common cause of death from progressive lung disease with no effective therapy besides lung transplantation. This is in large part due to the fact that the pathogenesis of IPF remains unclear. It is thought to mostly be a complex disorder involving a genetic predisposition and an environmental trigger. There are currently no assay systems for drug discovery or animal models for efficacy studies that truly recapitulate IPF.

To address these issues, we have generated and extensively characterized an induced pluripotent stem cell (iPSC) based in vitro disease model that closely phenocopies IPF in a dish. These cells scar spontaneously and progressively when cultured over several days. Live cell imaging, transcriptome analysis, atomic force microscopy, immunostaining, apoptosis assays and cytokine arrays were used to characterize these scars. We found that the progressive scarring is driven by signals that include damage associated molecular patterns that drive a robust pro-inflammatory response, leading to the observed fibrosis.

Using the model, we developed a primary phenotypic high throughput drug screening assay to identify compounds that would target one or more of the phenotypic characteristics of our model, such as increasing apoptosis of hyper-proliferative fibroblasts, targeting extracellular matrix interactions, or targeting the stiffness of the cells. We identified a small molecule that prevents the formation of fibrosis and resolves fibrosis that has already formed in the dish as well as in lung slice tissue cultures from IPF patients. The small molecule imparts its wound healing and anti-fibrotic effect by altering the ratio of metalloproteinases to tissue inhibitors of metalloproteinases, blocking secretion of damage associated molecular patterns, and activating TNF, IL-1 and interferon regulated genes including pentraxins (NPTX1 and PTX3). Pentraxins are endogenous regulators of tissue repair, that initiate the phenotypic switch of pro-inflammatory macrophages to pro-resolutive macrophages which accounts for the anti-fibrotic effect seen in our pre-clinical models of IPF.

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4:30
Effects of Manufacturing Process and Host Cell Impurities on Immunogenicty and Ocular Inflammation
 
Samuel Pine
Samuel Pine
Principal Scientist, Immunology
Allergan
About Speaker: A trained immunologist supporting biotherapeutic drug development, Samuel Pine works closely with drug safety scientists to develop novel protein therapeutics in a wide variety of therapeutic areas. His background in vaccinology and developing immuno... Read Full Bio 
 
 
Samuel Pine
Samuel Pine
Principal Scientist, Immunology
Allergan
 
About Speaker:

A trained immunologist supporting biotherapeutic drug development, Samuel Pine works closely with drug safety scientists to develop novel protein therapeutics in a wide variety of therapeutic areas. His background in vaccinology and developing immunogenicity methods allow him to contribute unique solutions to the pharmacokinetic and immunogenicity challenges associated with many specialized applications. Prior to Allergan, Samuel developed vaccines for a variety of infectious diseases at the Infectious Disease Research Institute, the HIV Vaccine Trial Network/Fred Hutchinson Cancer Research Center and Novartis. Dr. Pine received his BA in Molecular, Cellular and Developmental Biology at the University of California, Santa Cruz and his PhD in Pathobiology from the University of Washington

 
Abstract: Treatmen...Read More 

Treatment of ocular diseases by biotherapeutic proteins raises unique challenges. Intravitreal injection of a recombinant protein demands particularly low levels of impurities to avoid intraocular inflammation and the possibility of enhanced immunogenicit y. Non-clinical animals models present an opportunity to assess the tolerability of biologic pr oteins in the eye, but are labor intensive and may be confounded by the impact of immunogenicity.

Our recent work has focused on assessing the ability of cell-based methods to be used as surrogates for assessing intravitreal tolerability that is historically observed in rabbits given a single injection of a protein. By preparing samples of a biotherapeutic protein with several manufacturing processes we were able to assess to relationship of manufacturing and host cell impurities to ocular inflammation. Using the same samples in a panel of cell-based methods designed to measure innate immune responses, we were able to compare the relative sensitivity of in vivo and in vitro methods. Data from this assessment helps support the selection of in vitro methods for screening manufacturing batches and ranking candidate drugs. The utility of implementing cell-based methods in translational development plans will also be discussed.

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4:30
Mechanisms of Metabolic Programming in Macrophages
 
Daniel  McVicar
Daniel McVicar
Deputy Director, Center for Cancer Research
National Cancer Institute, NIH
About Speaker: Dr. McVicar earned his Ph.D. at the Medical College of Virginia in Richmond studying cell-based immunotherapy for Glioblastoma. He moved to the NCI for postdoctoral study with John O'Shea and John Ortaldo studying cell signaling in NK cells. He curre... Read Full Bio 
 
 
Daniel  McVicar
Daniel McVicar
Deputy Director, Center for Cancer Research
National Cancer Institute, NIH
 
About Speaker:

Dr. McVicar earned his Ph.D. at the Medical College of Virginia in Richmond studying cell-based immunotherapy for Glioblastoma. He moved to the NCI for postdoctoral study with John O'Shea and John Ortaldo studying cell signaling in NK cells. He currently serves as a Deputy Director for the Center for Cancer Research of NCI and as the Deputy Director for Basic Research within the Cancer and Inflammation Program. His laboratory studies the regulation of innate immune cells in cancer, most recently with an emphasis on the regulation of metabolic programming.

 
Abstract: Macropha...Read More 

Macrophages undergo dramatic metabolic reprogramming when stimulated with LPS. This reprogramming sets the metabolic stage for inflammatory function. Reprogrammed macrophages exhibit dramatic increases in glucose utilization and decreased oxidative phosphorylation. This shift toward glycolysis and away from utilization of fatty acid oxidation has been termed “Glycolytic Commitment”. Despite profound reprogramming the biochemical mechanisms associated with this commitment are still not fully understood. Here we discuss ongoing work dissecting the biochemical basis of macrophage glycolytic commitment. We describe a profound role for nitric oxide in the establishment of the glycolytic phenotype and detail the pathways and outcomes affected by NO. Attendees will learn the pathways affected during commitment, the sequence of events associated with reprogramming, the mechanisms involved in reprogramming, and the biochemical ramifications of reprogramming.

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4:55
Immunology Studies on Recombinant Human Factor VIII Fc Fusion Protein
 
Katalin Kis-Toth
Katalin Kis-Toth
Sr. Scientist, Hematology Research
Biogen
About Speaker: Immunologist working on the immune aspects of hemophilia and replacement therapies.... Read Full Bio 
 
 
Katalin Kis-Toth
Katalin Kis-Toth
Sr. Scientist, Hematology Research
Biogen
 
About Speaker:
Immunologist working on the immune aspects of hemophilia and replacement therapies.
 
Abstract: Prophyla...Read More 

Prophylactic replacement therapy with factor in hemophilia prevents bleeds and preserves joints, and is considered as optimal therapy for severe hemophilia A and B. The main complication of this treatment is the formation of inhibitors (neutralizing anti-factor VIII antibodies) in ~30% of severe hemophilia A patients. Further understanding of how the immune system responds to rFVIII is an ongoing effort in hemophilia research, and is crucial for providing insights into how some patients develop inhibitor antibodies while others do not, and how best to prevent or reverse inhibitor formation. The extended half-life recombinant factor VIII Fc fusion protein (rFVIIIFc) is an effective and safe therapy to prevent and control bleeding episodes. The Fc region of this molecule not only is responsible for increasing rFVIII half-life, but also seems to promote antigen-specific tolerance as shown in a preclinical animal model (Krishnamoorthy et al., Cell Immunol 2016), and suggested in immune tolerance induction case reports (Malec et al., Haemophilia 2016; Ragni et al., Haemophilia 2016). To characterize the interactions of the Fc portion of rFVIIIFc with the immune system, we are investigating the effects of rFVIIIFc specifically on antigen presenting cells (APCs). APCs express a variety of Fc receptors (FcRs) that can potentially bind rFVIIIFc. Depending on the events following FcR binding, the APCs could translate these signals to T cells, shaping their development and responses to rFVIII. This presentation will discuss rFVIIIFc engagement of Fc receptors on APCs, effects on APC effector function, and the subsequent influence of those APCs on T cell differentiation.

The data collected in this study will help to understand the immunological effects of rFVIIIFc fusion protein, and the mechanism by which this specific hemophilia A therapy may modulate the immune responses.

Keywords:
Hemophilia A, Factor VIII, Fc fusion protein, Immunotolerance, Antigen presenting cells

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4:55
On the Trail of Immune Oncology with Luminex and Simple Plex
 
Annie  Chatterjee
Annie Chatterjee
Field Applications Scientist
ProteinSimple
About Speaker: Annie Chatterjee received her Ph.D. in Molecular Biology from the University of Texas at Austin. She was a post-doc at UNC Chapel Hill and Paradigm Genetics after which she went on to GSK to work in Technology Development. She has been Field Applicat... Read Full Bio 
 
 
Annie  Chatterjee
Annie Chatterjee
Field Applications Scientist
ProteinSimple
 
About Speaker:

Annie Chatterjee received her Ph.D. in Molecular Biology from the University of Texas at Austin. She was a post-doc at UNC Chapel Hill and Paradigm Genetics after which she went on to GSK to work in Technology Development. She has been Field Applications Scientist for 15 years, supporting new technologies at companies such as Amersham, Whatman, GE Healthcare and now ProteinSimple.

 
Abstract: The conventional manual ELISA used to...Read More 

The conventional manual ELISA used to detect protein biomarkers in biological samples is poorly suited to precision medicine owing to its tedious process, analyte cross-reactivity, and poor reproducibility. Designed to eliminate these limitations, Simple Plex assays allow simultaneous measurement of 1-4 analytes with an accurate, low volume assay automated on the Ella instrument in an hour.
Dysregulation of pro-inflammatory cytokines is commonly associated with the presence of immune checkpoint molecules in tumors. Here we describe recent Immuno-Oncology studies evaluating the multi-analyte assay format for dynamic range, sensitivity, and reproducibility. Simple Plex acted as a bioanalytical platform to verify pro-inflammatory cytokines and expression of immune checkpoint targets in a variety of samples, including tumor cell lines and human plasma/serum. Results demonstrated consistent sensitivity at low picogram/mL levels with 10% CV or less, and a 4-5 log dynamic range across all sample types. Rapid assay setup led to large speed improvements versus ELISA by incorporating factory-generated standard curves, built-in triplicates for each sample, and elimination of manual washes. Simple Plex enabled more sensitive detection in ¼ the time and ¼ the sample of a standard ELISA for single or multiple biomarkers.
Benefits:
Biomarkers were measured with the Simple Plex assay run on Ella providing the following benefits
1. Automated Low Volume Immunoassays without the need to run standard curves
2. Ability to measure 1-4 analytes without cross-reactivity
3. Rapid assay set-up with time to result being approximately 1 hour
4. Provided consistent sensitivity at low picogram/mL levels with 10% CV or less, and a 4-5 log dynamic range across all sample types

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5:20
HLA Binding Immunogenicity of Protein Drugs
 
Alessandro Sette
Alessandro Sette
Center Head, Division Head, and Professor
La Jolla Institute for Allergy and Immunology
About Speaker: Dr. Alessandro Sette has devoted more than 30 years to understanding and measuring immune responses, and developing disease intervention strategies against cancer, autoimmunity, allergy, and infectious diseases. Dr. Sette laboratory is focused on the... Read Full Bio 
 
 
Alessandro Sette
Alessandro Sette
Center Head, Division Head, and Professor
La Jolla Institute for Allergy and Immunology
 
About Speaker:

Dr. Alessandro Sette has devoted more than 30 years to understanding and measuring immune responses, and developing disease intervention strategies against cancer, autoimmunity, allergy, and infectious diseases. Dr. Sette laboratory is focused on the study of the specific structures (epitopes) that the immune system recognizes, and uses this knowledge to define the immune signatures associated with protective immunity versus immunopathology.

Dr. Sette is the Head of LJI's Division of Vaccine Discovery. He created and directs since the early 2000s the Immune Epitope Database (IEDB), a freely available, widely used bioinformatics resource.Dr. Sette has a doctorate in Biological Sciences fr om the University of Rome and was a postdoctoral fellow at the National Jewish Center in Denver, Colorado. In 1988, Dr. Sette joined Cytel Corp. and in 1997 founded Epimmune, where was VP of Research and Chief Scientific Officer until 2002, when he joined LJI.

 
Abstract: Unwanted immune response against prot...Read More 

Unwanted immune response against protein therapeutics are a major concern, as they can reduce therapeutic efficacy or lead to adverse reactions. T cell responses are key in development of such responses, and are directed against immunodominant regions within the protein drug sequence, which are often associated with binding to several allelic variants of HLA class II molecules (promiscuous binders). Here, we report a computational strategy to predict such promiscuous binding immunogenic regions in a given protein sequence, coupled with automatic calculation of single amino acid substitutions with predicted reduced HLA binding. Since HLA binding is a necessary requisite for immunogenicity, it is predicted that these substitution would also be associated with reduced immunogenicity. To avoid the unintended creation of new HLA binding region in the regions neighboring the predicted epitope, the program also predicts the effect of any given substitution on those flanking peptides. The algorithm was derived based on experimental data from Erythropoietin (EPO) protein engineering 1. Further, the program was applied on Vatreptacog alpha, an engineered factor VII molecule that failed in clinical trial due to its immunogenicity issues. The program identified the immunogenic peptides containing the engineered residues (located at positions 291-305 and 296-310) and predicted the effect of amino acid substitutions of these two epitopes. Seven substitutions predicted to simultaneously reduce immunogenicity for both peptides were selected for experimental validation, together with controls with no predicted reduction in HLA binding capacity.

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5:20
Harnessing Anti-Pathogen Immune Responses to Recondition the Tumor Microenvironment
 
Ute Hoch
Ute Hoch
Executive Director
Nektar Therapeutics
About Speaker: ... Read Full Bio 
 
 
Ute Hoch
Ute Hoch
Executive Director
Nektar Therapeutics
 
About Speaker:
 
Abstract: The IL-2 pathway is a potent means of...Read More 

The IL-2 pathway is a potent means of expanding tumor-killing CD8 T cells. However IL-2 also stimulates regulatory T cells (Tregs). NKTR-214 is an engineered cytokine designed for sustained and biased signaling of IL-2 receptors, significantly tipping the balance in the tumor microenvironment to favor expansion of CD8 T and NK cells over Tregs. We will discuss the design of NKTR-214 and its unique mechanism of action. The agent is currently in Phase 1 for the treatment of solid tumors

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5:20
Networking Reception & Poster Session
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Day - 2 Tuesday, February 7, 2017
 
Immunogenicity & Immunotoxicity 2017
Immunogenicity Assessment of Novel Drug Candidates and Biosimilars
Todd Lester, BioAgilytix Labs
8:00
Characterization of Particulates to Help Mitigate or Reduce Immunogenicity
 
Amber Fradkin
Amber Fradkin
Associate Director, Particle Characterization Core Facility
KBI Biopharma
About Speaker: Amber received her Ph.D. in Chemical Engineering within the Pharmaceutical Biotechnology Program with a specialization in the field of immunogenicity of therapeutic protein aggregates at the University of Colorado at Boulder. Amber also holds a Maste... Read Full Bio 
 
 
Amber Fradkin
Amber Fradkin
Associate Director, Particle Characterization Core Facility
KBI Biopharma
 
About Speaker:

Amber received her Ph.D. in Chemical Engineering within the Pharmaceutical Biotechnology Program with a specialization in the field of immunogenicity of therapeutic protein aggregates at the University of Colorado at Boulder. Amber also holds a Masters in Science from the University of Colorado at Boulder plus a Bachelors of Science from the Colorado School of Mines. Amber currently holds the position of Associate Director at KBI Biopharma where she manages the Particle Characterization Core that specializes in analytical methods for quantifying, characterizing and identifying submicron, subvisible and visible particulates. Previously, at Amgen, Amber was a Scientist within the biomolecular structures and interactions group where she supported biophysical characterization of protein products with a specialty in subvisible particle characterization and identification. She managed a team of 5 to support all subvisible particle characterization for commercial and late stage clinical products and authored particle characterization sections of numerous regulatory filings. She has over 10 years of experience (6 years industry) with analytical method development and validation, protein refolding and purification, formulation and stability strategy, and protein biophysical characterization. Prior to Amgen, Amber’s experiences include analytical and formulationdevelopment for Merck & Co. and collaborations with BaroFold, Inc. to employ high hydrostatic pressure to refold proteins and control and characterize subvisible particles.

 
Abstract: Regulato...Read More 

Regulatory agencies have become increasingly concerned with the potential risk of immunogenicity of therapeutic protein produ cts related to protein aggregates and subvisible particulates. Concurrently, significant advances have been made in analytical technology for the characterization and identification of particles present pharmaceutical products. With these advances comes a tremendous amount of new data with which to characterize biologics, devices, and small molecules. Careful interpretation of data and in-depth understanding of the method limitations is of utmost importance for using complementary methods to characterize particle profiles. This presentation demonstrates how multiple particle techniques can be used to characterize therapeutic products and their particle populations. We provide case studies to highlight the advantages of particle methods for characterizing

  • A commercially available brand of filgrastim and its biosimilar
  • A commercially available Recombinate and its infusion system
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Immunotherapeutics & Immunomonitoring 2017
Lunch Session: Immunomonitoring & Novel High Throughput Technologies
Christian Capitini, University of Wisconsin School of Medicine and Public Health
8:00
The Use of in vitro Assays to Accelerate Cancer Immunotherapy Development
 
Sofie PattjIn
Sofie PattjIn
CTO
ImmunXperts SA
About Speaker: Sofie Pattijn (CTO and founder, ImmunXperts) has over 20 years of experience in the field of immunogenicity assessment (vacci nes and biotherapeutics) and in vitro assay development. She has extensive hands-on lab experience and has managed and coach... Read Full Bio 
 
 
Sofie PattjIn
Sofie PattjIn
CTO
ImmunXperts SA
 
About Speaker:

Sofie Pattijn (CTO and founder, ImmunXperts) has over 20 years of experience in the field of immunogenicity assessment (vacci nes and biotherapeutics) and in vitro assay development. She has extensive hands-on lab experience and has managed and coached several In Vitro teams over the last decade. From 2008 till 2013 she was Head of the In Vitro Immunogenicity group at AlgoNom ics (Ghent, Belgium) and Lonza Applied Protein Services (Cambridge, UK). Prior to that, she worked at Innogenetics, Belgium for over 15 years.

 
Abstract: During t...Read More 

During the last years, significant advancement has been made in the clinical application of cancer immunotherapies. Molecules directed against immune checkpoints and other agonists show great promise for treatment of a variety of malignancies. Next to CTLA-4 and PD-1 blockade, a wide range of therapeutics with the potential to reverse the tumor-induced suppression are under development.

Early evaluation of the effectiveness of candidate therapeutics and combination therapies can be done using mouse models and in vitro bioassays with mouse or human immune cells.

Mixed lymphocyte reaction assays using both innate cells and lymphoid cells mimic a real physiological T cell response and are widely used for the potency screening of candidate therapeutics. The use of different allogenic donor combinations can provide additional information on the profile of the responding population. An important factor for sensitive assays and consistent results is the quality of the primary immune cells. Other T cell assays such as antigen-specific recall activation assays can be used to evaluate the ability of test molecules to promote T cell responses. In addition to T cell assays, macrophage polarization assays are an essential tool to evaluate metabolic or other reprogramming functions of test compounds. The use of customized in vitro assays supports the candidate selection and functionality testing of new oncology leads.

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Cytokines & Inflammation 2017
Targeting Cytokines for Therapeutic Interventions
Kathrin Michelsen, Cedars Sinai Medical Center
8:00
Gene Therapy Approaches for Treating Autoimmune Diseases: Preclinical and Clinical Studies
 
Paul  Robbins
Paul Robbins
Professor
The Scripps Research Institute
About Speaker: Paul D. Robbins, Ph.D. is a Professor of Molecular Medicine at The Scripps Research Institute (TSRI) in Jupiter, Florida and director of the TSRI Center on Aging. Previously he was a Professor of Microbiology and Molecular Genetics, Director of Basic... Read Full Bio 
 
 
Paul  Robbins
Paul Robbins
Professor
The Scripps Research Institute
 
About Speaker:

Paul D. Robbins, Ph.D. is a Professor of Molecular Medicine at The Scripps Research Institute (TSRI) in Jupiter, Florida and director of the TSRI Center on Aging. Previously he was a Professor of Microbiology and Molecular Genetics, Director of Basic Research for the Molecular Medicine Institute and Co-Director of the Paul Wellstone Cooperative Muscular Research Center at the University of Pittsburgh School of Medicine as well as Interim Director of Molecular & Cellular Oncology at the University of Pittsburgh Cancer Institute. He received his B.A. from Haverford College, his Ph.D. from the University of California at Berkeley and worked as a post-doctoral fellow in the laboratory of Dr. Richard Mulligan at the Whitehead Institute for Biomedical Research at MIT. He has co-authored over 320 peer-reviewed manuscripts and 170 book chapters and reviews and has edited four books. He was a member of the NIH PathB Study Section, Chair of the Italian Telethon Scientific Review Committee and a member of the Telethon Scientific Advisory Board. He also was a member of the Scientific Review Board of National Gene Vector Laboratory and the Board of Directors of the American Society of Gene Therapy. He has co-founded two biotechnology companies and currently serves on the Scientific Advisory Boards of five biotechnology companies. Dr. Robbins’ research is focused on developing therapeutic approaches, including small molecules, biologics and stem cells, to treat autoimmune diseases as well as extend healthspan.

 
Abstract: Gene the...Read More 

Gene therapy approaches for treating autoimmune disorders such as rheumatoid arthritis and type I diabetes have shown significant efficacy in numerous animal models. The effective approaches include ex vivo methods involving genetically modified dendritic cells (DC), exosomes derived from genetically modified DC as well as direct, in vivo gene transfer of immunomodulatory cytokines to joints and to endogenous islets. We have performed several clinical trials for gene therapy of rheumatoid arthritis using intra-articular injection of genetically modified synovial fibroblasts expressing the interleukin-1 receptor antagonist protein (IL-1Ra). Currently we are developing adeno-associated virus (AAV)-based approaches for treating human and equine osteoarthritis by intra-articular gene transfer of IL-1Ra. We also have been evaluating the therapeutic efficacy of different immunosuppressive or anti-inflammatory molecules including members of the IL-12 family The significant pre-clinical and clinical progress made towards developing viable gene therapy approaches for treating autoimmune or inflammatory disorders diseases will be presented.

The benefits of the talk include an overview of gene therapy approaches for treating autoimmune, inflammatory and degenerative diseases, demonstration of efficacy in multiple preclinical models of arthritis including horses, an update on the status of clinical trials to treat both rheumatoid and osteoarthritis by gene therapy and discussion of novel immunosuppressive cytokines.

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8:25
Characterization of a Robust Non-Clinical Immune Response to a Bispecific Antibody Therapeutic
 
Kate Peng
Kate Peng
Senior Scientist and Project Lead
Genentech, Inc.
About Speaker: Dr. Kate Peng, received her Ph.D. in metabolic biology from the University of California, Berkeley. Following her postdoctoral trainings at Berkeley, Dr. Peng worked as a scientist/senior scientist in the biotechnology industry with a focus on develo... Read Full Bio 
 
 
Kate Peng
Kate Peng
Senior Scientist and Project Lead
Genentech, Inc.
 
About Speaker:

Dr. Kate Peng, received her Ph.D. in metabolic biology from the University of California, Berkeley. Following her postdoctoral trainings at Berkeley, Dr. Peng worked as a scientist/senior scientist in the biotechnology industry with a focus on developing a series of cell-based high-throughput screening assays to monitor GPCR activation. Dr. Peng joined Genentech in 2007 and is currently a senior scientist in the Assay Development & Technology (ADT) group of BioAnalytical Sciences (BAS) department. Her focus is on development of bioanalytical strategies and methods to enable assessment of the immunogenicity, pharmacokinetics and pharmacodynamics of protein bio-therapeutics from early development to clinical as well as post-marketing studies. Dr. Peng has led bioanalytical effort for supporting the development of molecules that target immunology, neurology and cardiovascular disease areas.

 
Abstract: Bivalent...Read More 

Bivalent monoclonal antibody (mAb) therapeutics have had substantial impact in treatment of variety of diseases in the clinic. Bispecific mAbs (bsmAbs) are a novel class of mAbs that aim to improve drug efficacy by simultaneously working on two targets, therefore have garnered recent attention and are in clinical trials for several diseases. However, this is a relatively new approach with limited literature in clinical and non-clinical settings. Anti-A/B is a bsmAb therapeutic that targets molecules A and B, which are implicated in the pathogenesis of autoimmune diseases. In a multiple dose cynomolgus monkey toxicology study, unexpected high incidence and magnitude of anti-therapeutic antibody (ATA) responses was observed. Characterization of the observed ATA responses was conducted to understand the gross immune dominant epitope(s) of anti-A/B. This presentation discusses our strategy for assessing the ATA responses to the bsmAb and summarizes the characterization results as well as the impact of ATAs on the toxicokinetics/pharmacodynamics (TK/PD) profiles of anti-A/B. Whether the strong immune responses to anti-A/B observed in cynomolgus monkeys is translatable to the clinic will also be discussed based on the preliminary clinical study results.

Key words:
immunogenicity, bispecific monoclonal antibody, immune dominant epitope characterization, toxicokinetics/pharmacodynamics, bridging ELISA

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8:25
TL1A, A Member of the TNF Superfamily, in Inflammatory Bowel Diseases
 
Kathrin  Michelsen
Kathrin Michelsen
Assisstant Professor, Department of Medicine
Cedars Sinai Medical Center
About Speaker: Kathrin Michelsen, PhD, is an assistant professor of medicine and research scientist in the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute in the Department of Medicine at Cedars-Sinai. She is also an adjunct associate ... Read Full Bio 
 
 
Kathrin  Michelsen
Kathrin Michelsen
Assisstant Professor, Department of Medicine
Cedars Sinai Medical Center
 
About Speaker:

Kathrin Michelsen, PhD, is an assistant professor of medicine and research scientist in the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute in the Department of Medicine at Cedars-Sinai. She is also an adjunct associate professor at the University of California, Los Angeles, David Geffen School of Medicine. She earned a master's degree in biopharmacology and toxicology from the University of Greifswald, Germany. Michelsen holds a doctorate in molecular biology from the Humboldt University of Berlin, Germany. After she earned her PhD, Michelsen engaged in postdoctoral training in immunology at Cedars-Sinai. She became a faculty member of the Department of Medicine in 2006.

Michelsen is a member of several professional organizations including the American Association of Immunologists, International Endotoxin and Innate Immunity Society and Society for Mucosal Immunology. She has authored or co-authored more than 40 peer-reviewed manuscripts and book chapters.

 
Abstract: The TNF ...Read More 

The TNF family member TL1A plays an important role in the development of inflammatory bowel diseases (IBD) by modulating TH1, TH17, and TH2 responses. TL1A polymorphisms have been identified through genome-wide association studies to confer susceptibility to IBD and have been associated with disease severity. IBD patients with TL1A risk haplotypes have elevated expression of TL1A in peripheral blood monocytes and transgenic mice overexpressing TL1A develop spontaneous small intestinal inflammation. However, the effects of TL1A on other TH subsets remain unknown. Recently, TH9 cells have been identified as an independent TH cell subset and have been implicated in allergic lung inflammation, and IBD. We describe a novel role for TL1A as a strong inducer of TH9 cell differentiation. We will describe the signaling pathways involved in TL1A-induced TH9 cell differentiation. Utilizing an adoptive T cell transfer model of colitis we demonstrate that TH9 cells differentiated in the presence of TL1A are highly pro-inflammatory in vivo and lead to severe intestinal and lung inflammation as characterized by increased cell numbers in mesenteric lymph nodes and spleens, enhanced proliferation of transferred cells, and increased IL-9, IL-13, and IL-17 production. Our results demonstrate that TL1A promotes TH9 cell differentiation and function and define a role for IL-9 in TL1A-induced mucosal inflammation and potential therapeutic target in inflammatory diseases.

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8:50
Reporter-Gene Assay for Patient Monitoring of Infliximab Biological Activity and Immunogenicity: 3 Years of Clinical Experience
 
Eszter Lazar-Molnar
Eszter Lazar-Molnar
Immunology Medical Director
ARUP Laboratories
About Speaker: Dr. Lazar-Molnar is an assistant professor in the Department of Pathology at the University of Utah School of Medicine. She received her PhD in biological sciences at the Semmelweis University in Budapest, Hungary and completed a postdoctoral fellows... Read Full Bio 
 
 
Eszter Lazar-Molnar
Eszter Lazar-Molnar
Immunology Medical Director
ARUP Laboratories
 
About Speaker:

Dr. Lazar-Molnar is an assistant professor in the Department of Pathology at the University of Utah School of Medicine. She received her PhD in biological sciences at the Semmelweis University in Budapest, Hungary and completed a postdoctoral fellowship in the laboratory of Dr. Stanley G. Nathenson at the Albert Einstein College of Medicine in Bronx, New York, where she was studying immune regulation through costimulatory molecules and finding new ways for designing immunotherapy. She was the recipient of a Cancer Research Institute postdoctoral fellowship and the Belfer Outstanding Postdoctoral Research Award in 2009. She completed a clinical immunology fellowship at the University of Utah and is currently a medical director in Immunology at ARUP and assistant director of the Histocompatibility & Immunogenetics Laboratory at the University of Utah. Her research interests include cellular immunology, immunotherapy, and transplantation immunology. Dr. Lazar-Molnar is board certified by the American Board of Medical Laboratory Immunology (ABMLI) and American Board of Histocompatibility and Immunologenetics (ABHI).

 
Abstract: TNF-&alp...Read More 

TNF-α antagonists such as infliximab are used for the treatment of inflammatory bowel disease and other inflammatory and autoimmune diseases. Development of an immune response and subsequent neutralizing antibodies against these protein-based drugs is a major impediment that contributes to therapeutic failure, or adverse effects such as hypersensitivity reactions. Rational and cost-effective evaluation of clinical non-responsiveness includes measurement of serum drug levels, and detection of drug-specific antibodies. This presentation summarizes results of 3 years of clinical laboratory experience using a functional, cell-based reporter gene assay (RGA) developed for measuring the biological activity and neutralizing antibody response to serum infliximab. Results are presented from over 10,000 clinical specimens from patients suspected of therapeutic failure. In contrast to binding assays, which detect an overall antibody response, the RGA specifically detects those antibodies that have drug-neutralizing function, and thus, pose higher risk for therapeutic failure. The RGA is currently the only functional clinical test available to measure serum infliximab activity, and neutralizing antibodies. Due to its accuracy and precision, and suitability for high-throughput testing, this robust platform can be applied to any TNF-α antagonist, providing an invaluable tool for the clinical management of patients with treatment failure.

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8:50
CD8+ T Cell Activation and Objective Responses in Patients Receiving PEGylated Human IL-10 (AM0010)
 
Martin  Oft
Martin Oft
VP Preclinical & Clinical Research
Armo Biosciences
About Speaker: Martin Oft is Co-founder and VP pre-clinical and clinical R&D at ARMO BioSciences in Redwood City His research focuses on the discovery of novel mechanism in immuno-oncology, including mechanisms of CD8+ T cell activation and the regulation of pr... Read Full Bio 
 
 
Martin  Oft
Martin Oft
VP Preclinical & Clinical Research
Armo Biosciences
 
About Speaker:

Martin Oft is Co-founder and VP pre-clinical and clinical R&D at ARMO BioSciences in Redwood City His research focuses on the discovery of novel mechanism in immuno-oncology, including mechanisms of CD8+ T cell activation and the regulation of pro-inflammatory vs. pro-cytotoxic immune responses in cancer. He currently oversees clinical studies with PEGylated IL-10 in solid tumors.

 
Abstract: IL-10 is...Read More 

IL-10 is known as an anti-inflammatory and immune inhibitory cytokine, but IL-10 also stimulates CD8+ T cells toxicity and proliferation. IL-10 and IL-10 receptor deficient mice and men develop inflammatory bowel disease and cancer. In mouse cancer models, PEGylated IL-10 (AM0010) enhances tumor specific CD8 T cell expansion and cytotoxicity. Tolerability and efficacy of AM0010 alone and in combination with immune checkpoint inhibitors was evaluated in a phase 1 study. AM0010 monotherapy induced objective tumor responses in RCC, melanoma and cutaneous T cell lymphoma. AM0010 in combination with anti-PD-1 showed improved response rates in RCC (n=8) or NSCLC (n=5) (ORR 50 and 40% respectively).

Patients receiving AM0010 had a systemic and sustained elevation of Th1 and Th2 type cytokines in the serum, as well as increased cytotoxicity mediating products of CD8+ T cells. Th17 related cytokines, which mediate chronic inflammation and may promote tumor progression in cancer patients were reduced. In-vitro, TCR ligation increased both, the immune checkpoints PD-1 and Lag-3 on CD8+ T cells and the expression of the IL-10 receptor. AM0010 induced the phosphorylation STAT3 (p-STAT3) preferentially in TCR activated CD8+ T cells, increased the proliferation of PD-1+ CD8+ T cells and the expression of Granzyme in those cells.

In patients, AM0010 induced an expansion and proliferation of PD1+ Lag-3+ CD8+ T cells in the blood and an increase of CD8+ T cells in the tumor. The expansion of PD-1+ Lag-3+ CD8+ T cells was correlated with objective tumor response. CD8 T cells and the expression of GranzymeB, p-STAT3 or Lag-3 in the tumor infiltrating CD8+ T cells were increased. AM0010 treatment also resulted in the progressive systemic expansion of novel T cell clones, which were not detectable in the patient prior to treatment. This de-novo expansion coincided with tumor responses correlated and with objective tumor responses.

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9:15
Predicting, Avoiding and Reducing the Risk of Failure when Developing Biotherapeutics
 
Yvette Stallwood
Yvette Stallwood
Head, Applied Protein Services
Lonza Biologics
About Speaker: Yvette Stallwood completed her PhD at the University of Birmingham (UK) and joined Lonza in 2007. Dr Stallwood has been Head of Applied Protein Services for fiveyears. The Applied Protein Services team are focussed on the development and provision of... Read Full Bio 
 
 
Yvette Stallwood
Yvette Stallwood
Head, Applied Protein Services
Lonza Biologics
 
About Speaker:

Yvette Stallwood completed her PhD at the University of Birmingham (UK) and joined Lonza in 2007. Dr Stallwood has been Head of Applied Protein Services for fiveyears. The Applied Protein Services team are focussed on the development and provision of services to support the development of new biotherapeutic proteins and vaccine candidates, including immunogenicity assessment and screening, manufacturing assessment and protein production.

 
Abstract: This pre...Read More 

This presentation will discuss how in silico and in vitro methodologies are employed to perform an immunogenicity and developability risk assessment in order to highlight potential risks of failure for the development of biotherapeutics. In silico methods can be used to evaluate protein sequence and structure to assess the likelihood of immunogenic responses and potential manufacturability issues including aggregation and PTMs. Ex vivo T and B-Cell responses enable the assessment of overall immunogenicity risks; different approaches are highlighted to further identify processed and presented epitopes.

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9:15
Targeting the HVEM-CD160-BTLA Network in Immunity
 
John  Sedy
John Sedy
Research Assistant Professor, Infectious and Inflammatory Disease
Sanford Burnham Prebys Medical Discovery Institute
About Speaker: Dr. John R. Sedy is an investigator with extensive training and experience in immunology research. Dr. Sedy received his Ph.D. in Immunology from Washington University in Saint Louis, Missouri where he first began studying the factors that prevent au... Read Full Bio 
 
 
John  Sedy
John Sedy
Research Assistant Professor, Infectious and Inflammatory Disease
Sanford Burnham Prebys Medical Discovery Institute
 
About Speaker:

Dr. John R. Sedy is an investigator with extensive training and experience in immunology research. Dr. Sedy received his Ph.D. in Immunology from Washington University in Saint Louis, Missouri where he first began studying the factors that prevent autoimmune disease, now known as immune checkpoint proteins. Dr. Sedy first began postdoctoral training at the La Jolla Institute for Allergy and Immunology and then at the Sanford Burnham Prebys Medical Discovery Institute with Dr. Carl F. Ware where he made important discoveries describing how the responses of immune cells to infection and inflammation are naturally controlled, and what kind of interventions may lead to novel disease therapeutics.

In 2013, Dr. Sedy was appointed as a Research Assistant Professor at SBP to pursue development of therapeutics for autoimmune disease. In recognition of his work, Dr. Sedy was also granted awards from the National Psoriasis Foundation and the American Heart Association to fund his research in psoriasis and in multiple sclerosis disease. Dr. Sedy has presented this work at numerous international conferences. Dr. Sedy holds multiple patents on potential therapies for immune checkpoint proteins, and importantly, he has worked with Dr. Ware to partner with biopharma in the development of potential therapeutics, successfully combining basic science research with translational medicine. Dr. Sedy continues to develop his research in collaboration with several groups at SBP to understand what role the immune system plays in a variety of human diseases including cancer, and how to harness it to control disease progression.

 
Abstract: The TNF ...Read More 

The TNF receptor superfamily member Herpesvirus entry mediator (HVEM; TNFRSF14) broadly regulates immune responses in multiple cell types through ligand interactions with the TNF cytokines LIGHT (TNFSF14) and Lymphotoxin-? (LTA), and the immunoglobulin domain containing receptors B and T Lymphocyte Attenuator (BTLA) and CD160. HVEM costimulates lymphocytes when activated by each of these ligands, while HVEM activation of BTLA limits T cell activation, proliferation, and effector function. In addition, BTLA regulates IL-7-dependent homeostasis of ?? T cells and innate lymphoid cells (ILC), as well as IL-7-induced expression of IL-17 and TNF-?. CD160 has been demonstrated to inhibit activation of T cells, while in natural killer (NK) cells CD160 promotes the expression of inflammatory cytokines and effector function. In human B cell lymphoma HVEM missense mutations localized to the extracellular domain, resulting in preferential loss of CD160 and BTLA interactions compared to LIGHT, and were associated with alterations in cytotoxic effector cell signatures within tumor biopsies. Mutated HVEM proteins retained the capacity to inhibit T cell signaling through BTLA, while reducing costimulation of NK cell cytolysis through CD160. Based on these findings, we developed a high affinity BTLA-specific HVEM mutein agonist that shows potent inhibitory activity in lymphocytes, thus indicating a route for anti-inflammatory therapy in autoimmune disease.

  • Background on the HVEM-BTLA-CD160-LIGHT regulatory network in lymphocytes
  • BTLA regulation of cytokine pathways in ?? T cells
  • Mutation of HVEM in lymphoma and the impact on ligand binding
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9:40
Morning Networking Break
9:40
Morning Networking Break
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10:10
A Novel System for Improved Quantification of ADCC Activity of Therapeutic Antibodies
 
Michael Tovey
Michael Tovey
INSERM Director, Research, Laboratory of Biotechnology & Applied Pharmacology
Biomonitor
About Speaker: Michael G. TOVEY, Ph.D, is mt@INSERM Director of Research in the Laboratory of Biotechnology and Applied Pharmacology, CNRS UMR 8113 at the Ecole Normale Supérieure, Cachan, France. He is the author of more than 250 articles on cytokines, biotechnol... Read Full Bio 
 
 
Michael Tovey
Michael Tovey
INSERM Director, Research, Laboratory of Biotechnology & Applied Pharmacology
Biomonitor
 
About Speaker:

Michael G. TOVEY, Ph.D, is mt@INSERM Director of Research in the Laboratory of Biotechnology and Applied Pharmacology, CNRS UMR 8113 at the Ecole Normale Supérieure, Cachan, France. He is the author of more than 250 articles on cytokines, biotechnology, and immunogenicity. He is a member of numerous scientific boards. He is chair of the International Cytokines Standards Committee, and a member of the European Adjuvant Advisory Committee. He is editor -in-chief of Detection and Quantification of Antibodies to Biopharmaceuticals, Associate Editor of Cytokine, Associate Editor of the Journal of Interferon and Cytokine Research, Associate Editor of The Scientific World Journal and a member of the Editorial Board of the Journal of Immunoassay & Immunochemistry. He is chair of Coral Gables Symposia.or

 
Abstract: The acti...Read More 

The activity of a number of therapeutic antibodies is mediated in part by antibody-dependent cell-mediated cytotoxicity (ADCC). Traditional methods for quantifying ADCC activity are labor intensive and have a high level of inherent variability due in part to the use of primary human NK-cells from different donors as the effector cells. Although these limitations have been partially addressed by the use of an engineered effector cell line expressing the low affinity Fc receptor, FcγRIIIa (CD16), that responds to ligation of the Fc moiety of antibody bound to the specific antigen expressed on target cells by activation of a NFAT responsive reporter gene nevertheless there is a need for an improved ADCC assay. A novel recombinant effector cell line has been developed in which the firefly luciferase reporter gene is regulated by a synthetic chimeric promoter that confers improved sensitivity, an improved dynamic range, an improved tolerance to human serum and a reduced incubation time, relative to engineered effector cell lines that express a NFAT regulated reporter-gene, when used in an ADCC assay together with engineered target cells. Novel target cells, together with homologous control cells, have been developed for the quantification of the ADCC activity of rituximab, trastuzumab. cetuximab and TNFα antagonists. The ADCC activity of the TNFα antagonist infliximab has been quantified in serum samples from patients with Crohn’s disease and that of adalimumab and etanercept in patients with rheumatoid arthritis with a high degree of precision and with minimal interference from human serum

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Immunotherapeutics & Immunomonitoring 2017
Combination Immunotherapy
William Redmond, Earle A. Chiles Research Institute
10:10
Rational Design of Immunotherapy Clinical Trials
 
John  Janik
John Janik
Professor of Medicine, Director of Cancer Center Immune Therapy Clinical Trial Program
Augusta University
About Speaker: Dr. Janik is a Professor of Medicine and the Director of the Immune Therapy Clinical Trial Program at the Georgia Cancer Center at Augusta University. He is an expert in translational research of biological response modifiers and in hematologic malig... Read Full Bio 
 
 
John  Janik
John Janik
Professor of Medicine, Director of Cancer Center Immune Therapy Clinical Trial Program
Augusta University
 
About Speaker:

Dr. Janik is a Professor of Medicine and the Director of the Immune Therapy Clinical Trial Program at the Georgia Cancer Center at Augusta University. He is an expert in translational research of biological response modifiers and in hematologic malignancies. He has extensive clinical trial experience in the use of cytokines, armed and unarmed monoclonal antibodies, hematopoietic growth factors, cellular based therapies and chemotherapy in the treatment of patients with advanced malignancy. He participated in the translational studies of interleukin 1 alpha as a chemo-protective agent in patients treated with high dose chemotherapy and was a recipient of the NIH Merit Award for this study that was the first demonstration of an agent to improve platelet recovery following chemotherapy. While in the Metabolism Branch of the National Cancer Institute he developed the initial trial of ipilimumab in the treatment of hematologic malignancies, participated in the first trial of anti-transforming growth factor beta in melanoma and renal cell cancer, novel vaccine therapies and CD19 chimeric antigen receptor T cell therapy. He also developed the clinical protocol for the use of nivolumab in Hodgkin’s Lymphoma while at Bristol-Myers Squibb. Dr. Janik has over 90 peer-reviewed publications primarily in the areas of immunotherapy of cancer and hematologic malignancy.

 
Abstract: Understa...Read More 

Understanding the pathways of T cell receptor and co-receptor signaling will be essential for optimal use of immunotherapy agents in the clinic. Although great success has been observed with agents that interfere with the interaction of PD-1 and PD-L1 in many tumor types, the next steps in combination immunotherapy remain unknown. The mechanism of action of checkpoint inhibitors such as ipilimumab, anti-LAG3 and anti-TIM3 suggest that their combination will be straight forward. The improved response rates of the combination of antibodies that block the CTLA4 and PD-1 pathways however come with increased toxicity but other checkpoint inhibitors may produce less toxicity while still improving response rates. There are also clues to suggest that agents that preserve T cell memory in a “stem cell” state will enhance checkpoint inhibitor therapy. The combination of MEK inhibition with atezolizumab produced a 20% response rate in micro satellite stable colon cancer whereas no response would have been expected with PD-1/PD-L1 blockade alone. More difficult to consider however are combinations of T cell agonists with checkpoint inhibitors. The optimal dose and schedule for administration of anti-OX40 in animals and preliminary data from patients with cancer suggest that there will be an optimal biologic dose for its use. Furthermore whether this optimal dose can be combined with agents that interfere with PD-1/PD-L1 signaling are unclear to improve response rates is under investigation. I will discuss preclinical rationales for the use of combination immunotherapy and potential problems that may be encountered.

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10:10
Targeting the IL-7R Pathway in Leukemi
 
Scott  Durum
Scott Durum
Chief, Section of Cytokines and Immunity
NIH - National Cancer Center - Center for Cancer Research
About Speaker: Scott Durum trained in immunology at Wake Forest, Oak Ridge, National Jewish and Yale before coming to the National Cancer Institute, National Institutes of Health. His lab has been interested in the IL-7 pathway for a number of years. Recently, toge... Read Full Bio 
 
 
Scott  Durum
Scott Durum
Chief, Section of Cytokines and Immunity
NIH - National Cancer Center - Center for Cancer Research
 
About Speaker:

Scott Durum trained in immunology at Wake Forest, Oak Ridge, National Jewish and Yale before coming to the National Cancer Institute, National Institutes of Health. His lab has been interested in the IL-7 pathway for a number of years. Recently, together with collaborators, they found that this is a major pathway driving Acute Lymphoblastic Leukemia, the most common cancer in children. They are working to develop therapeutics directed against the IL-7 pathway in this disease.

 
Abstract: Acute ly...Read More 

Acute lymphoblastic leukemia, derived from immature T or B cells, is the most common cancer in children. Current chemotherapeutic regimen are effective in over 80% of T-ALL, but the failure rate and the harshness of current treatments makes new approaches desirable. We and others have recently identified gain-of-function mutations in IL-7R alpha which serve as driver oncogenes in T cell acute lymphoblastic leukemia (T-ALL). Most of these mutations consist of insertions containing cysteine into the juxtamembrane region, creating homodimers. These signal independently of IL-7 or the gamma-c chain of the IL-7 receptor, and constitutively activate Jak1. Two approaches have been undertaken to target the IL-7R pathway in T-ALL: inhibition of Jak1, and development of monoclonal antibodies (MAbs) against IL-7R alpha. Ruxolitinib is a recently FDA approved inhibitor of Jak1, and we show it is an effective inhibitor of cells driven by mutant IL-7Ralpha in vitro and in immunodeficient mice. Two novel mouse MABs were developed that are directed against two different epitopes on human IL-7Ralpha, and they recognize both mutant and WT proteins. MAbs were chimerized with human IgG1 to optimize antibody-dependent cell mediated cytotoxicity (ADCC). These MAbs were highly effective in ADCC assays, mediating NK cell killing of T-ALL cells harboring mutant IL-7R alpha, and in xenografts of patient T-ALL cells with mutant or WT IL-7R. These approaches are being developed as new therapeutics for acute lymphoblastic leukemia, most of which use the IL-7R pathway either through normal ligand signaling or mutations in the pathway

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10:35
Development of Neutralizing Antibody Assay
 
Lynn Kamen
Lynn Kamen
Scientist, BioAnalytical Sciences
Genentech, Inc.
About Speaker: Lynn Kamen received her Ph.D. in Immunology at the University of Michigan where she used innovative microscopy methods to study phosphoinositide signaling during Fc receptor-mediated phagocytosis in macrophages. She completed her postdoctoral fellows... Read Full Bio 
 
 
Lynn Kamen
Lynn Kamen
Scientist, BioAnalytical Sciences
Genentech, Inc.
 
About Speaker:

Lynn Kamen received her Ph.D. in Immunology at the University of Michigan where she used innovative microscopy methods to study phosphoinositide signaling during Fc receptor-mediated phagocytosis in macrophages. She completed her postdoctoral fellowship at the University of California San Francisco where she continued her investigation of signaling pathways controlling innate immune cell function. Lynn transitioned her work on innate immune cell activation and inflammation at Portola Pharmaceuticals, where she helped to characterize the mechanism of action of a small molecule kinase inhibitor of Syk. In her current role in BioAnalytical Sciences at Genentech, her group is responsible for all effector function and cell-based assays that support in vitro biological characterization and immunogenicity assessment of antibody therapeutics.

 
Abstract: Assessin...Read More 

Assessing the immunogenicity of a therapeutic protein product is essential when determining its safety and efficacy. For many years, use of an ATA (anti-therapeutic antibody) assay was the primary means of determining the immune response to a biological therapy. High ATA titers combined with a drop in PK, could serve as an explanation as to why there might be an observed lack of efficacy. More recently, NAb (neutralizing antibody) assays have been used in conjuction with traditional ATA assays to gain a better understanding of the immunogenicity response. A NAb assay is designed to specifically detect only the anti-therapeutic antibodies that block the function of the therapeutic. Since a positive NAb response can directly correlate with a drop in efficacy, the NAb assay can be a very powerful tool to gain insight about not only immunogenicity, but the expected efficacy of the therapeutic. Ther efore, proper design of the NAb assay is essential to be able to gain the most accurate immunogenicity information. T his talk will review the different strategies involved in developing a robust NAb assay. The first consideration for developing a NAb assay should be format selection. Dependent upon the therapeutic target, the assay could be a cell-based assay, a ligand binding ELISA, or an enzymatic readout. The second consideration in developing a NAb assay is the selection of the positive control, which serves as a surrogate for the neutralizing antibody. The positive control helps to determine both the sensitivity and drug tolerance of the assay. The final consideration in developing a NAb assay is matrix tolerance. The assay should be designed to withstand the sample matrix, but sample pretreatment can be used if matrix tolerance proves to be an issue. A robust neutralizing antibody assay can serve as a meaningful tool for interpreting the immunogenicity and efficacy of a novel therapeutic.

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10:35
The Role and Function of the IL-33/ST2 Axis in Gut Health and Disease
 
Theresa  Pizarro
Theresa Pizarro
Professor
Case Western Reserve University
About Speaker: After receiving an undergraduate degree in Psychology/Biology at Case Western Reserve University (CWRU) in Cleveland, OH, Theresa Pizarro entered the graduate program at Loyola University Chicago in the Department of Cell Biology, Neurobiology & ... Read Full Bio 
 
 
Theresa  Pizarro
Theresa Pizarro
Professor
Case Western Reserve University
 
About Speaker:

After receiving an undergraduate degree in Psychology/Biology at Case Western Reserve University (CWRU) in Cleveland, OH, Theresa Pizarro entered the graduate program at Loyola University Chicago in the Department of Cell Biology, Neurobiology & Anatomy, where she obtained her Ph.D. focused on transplant immunology in 1993. She then completed a postdoctoral fellowship in mucosal immunology at the University of Southern California/LAC Medical Center in Los Angeles, and began her career in academia in 1995 as faculty in the Department of Medicine at the University of Virginia (UVA) in Charlottesville, VA. She remained at UVA for 13 years and rose to the rank of tenured Associate Professor before returning to CWRU in 2009 as faculty in the Department of Pathology. In 2005-06, she spent a one-year sabbatical as Visiting Professor, studying common immunological pathways between inflammatory bowel disease and autoimmune liver disease at the Università degli Studi di Firenze in Florence, Italy, where she continues to be a member of the “denothe” Research Center of Excellence. Dr. Pizarro has served and currently serves on numerous NIH study sections, the ERC review panel for Immunity & Infection, and foundation scientific review panels, including the Crohn’s & Colitis Foundation of America (CCFA), where she is currently the Co-Chair of the Senior Research Awards Committee. She has sat on several editorial boards for GI-related journals, and is an active member of the American Gastroenterological Association (AGA), where she has served on several committees, including the Women’s Taskforce and Committee on Gastroenterology Research, as well as serving as Basic Science Councilor for the Inflammation, Microbiology & IBD Section of the AGA. She has been recognized for her scientific contributions by the Women’s & Diversity in Science Committee of the Society for Leukocyte Biology as a featured scientist, and as the recipient of the 2013 DeGregorio Foundation Award. Dr. Pizarro is currently a tenured Professor in the Department of Pathology with a secondary appointment in Medicine at CWRU.

 
Abstract: IL-33, also known as IL-1F11, is the ...Read More 

IL-33, also known as IL-1F11, is the newest member of the IL-1 family and was initially associated with the development of Th2 immunity, based on the expression of its cell-bound receptor, ST2L (IL-1R4), on polarized Th2 lymphocytes and more recently, on innate lymphoid cells, as well as its ability to potently induce Th2 cytokine production in both in vitro and in vivo systems. IL-33 is upregulated in inflammatory bowel disease (IBD) and has the ability to potently induce Th2 immune responses and simultaneously amplify Th1-mediated inflammation.  However, although a clear association has been established between IL-33 and IBD, mechanistic studies to date have yielded ambiguous results, with IL-33 possessing both pathogenic as well as protective functions. Similarly, while the IL-33/ST2 axis has also been recently implicated in colorectal cancer and dysregulated epithelial alterations, this ligand-receptor pair has also been shown to be important in intestinal epithelial regeneration and wound healing. The presentation will attempt to mechanistically reconcile the precise role of IL-33 during health and disease, dissecting the dichotomous role of this novel cytokine system. Overall, investigation of the IL-33/ST2 axis has provided a new body of information, producing novel pathogenic hypotheses for the development of chronic gut disorders that have important translational implications, both in regard to the prevention as well as the treatment of patients suffering GI-related disease, including colorectal cancer and IBD.

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11:00
Round Table Discussions
11:00
Round Table Discussions
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11:50
Lunch Provided by GTCbio
11:50
Lunch Provided by GTCbio
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Immunogenicity & Immunotoxicity 2017
Immunogenicity Assessment of Novel Drug Candidates and Biosimilars (Cont’d)
Michelle Krogsgaard, The Perlmutter Cancer Center at NYULMC
12:50
Preclinical Methods to Evaluate Potential in Vivo Immunogenicity Risk of Biotherapeutics
 
Mark Fogg
Mark Fogg
Immunology Group Leader
Abzena
About Speaker: Mark Fogg, Ph.D., leads the Immunology Group at Abzena. Abzena provides proprietary technologies and complementary services to organisations involved in the development of biopharmaceutical products. The Immunology group has historically performed va... Read Full Bio 
 
 
Mark Fogg
Mark Fogg
Immunology Group Leader
Abzena
 
About Speaker:

Mark Fogg, Ph.D., leads the Immunology Group at Abzena. Abzena provides proprietary technologies and complementary services to organisations involved in the development of biopharmaceutical products. The Immunology group has historically performed varied immunological assays for the risk assessment of in vivo immunogenicity for biotherapeutics. More recently the group has diversified its offerings by encompassing a wider field of immunology services to support vaccine development and immune-oncology. Mark obtained his PhD in T cell immunology at the University of Reading, and carried out his postdoctoral work on vaccines for persistent virus infections and cancer immunotherapy including the generation of autologous tumor specific T cells for treatment of head and neck cancer at Harvard Medical School/DFCI/BW H. He then moved to Pfizer to work within Clinical R&D on precision medicine and biomarker discovery for inflammatory diseases prior to progressing to Abzena.

 
Abstract: ...Read More 
Multiple methods can aid ranking and selection of lead molecules during the preclinical phase for molecules with a reduced risk of clinical immunogenicity. The assays range from in silico algorithms to predict likelihood of sequences binding to MHC class II alleles to in vitro assays using primary human cells. Peptides derived from biotherapeutics that have undergone native antigen processing and selection for binding to MHC class II molecules in vitro may be eluted and characterised by Mass Spectrometry to show the potential repertoire of peptides available for recognition by the immune response. On top of this, assays that measure naive T cell proliferation and cytokine responses may be used to demonstrate immune recognition of peptides, adding an additional layer of confidence. Combining these assays in an appropriate format allows re-engineering of biotherapeutics to remove potential MHC class II binding sequences, ranking of biotherapeutics, and selection of molecules to mitigate clinical immunogenicity risk of biotherapeutics.
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Cytokines & Inflammation 2017
Influence & Regulation of the Microbiome on Immune Responses
Anna Di Nardo, University of California, San Diego
12:50
Commensal Microbiota and the Eye
 
Rachel  Caspi
Rachel Caspi
Chief, Immunoregulation Section
NEI, NIH
About Speaker: Dr. Caspi is is a tenured senior investigator, Section Head and Chief of the Laboratory of Immunology, National Eye Institute, NIH. She also holds an Adjunct Professorship at the University of Pennsylvannia Sch. Med. Dr. Caspi's research centers on i... Read Full Bio 
 
 
Rachel  Caspi
Rachel Caspi
Chief, Immunoregulation Section
NEI, NIH
 
About Speaker:

Dr. Caspi is is a tenured senior investigator, Section Head and Chief of the Laboratory of Immunology, National Eye Institute, NIH. She also holds an Adjunct Professorship at the University of Pennsylvannia Sch. Med. Dr. Caspi's research centers on immunology of the eye. A major direction is tolerance and autoimmunity to immunologically privileged retinal antigens in animal models of autoimmune uveitis, a potentially blinding human disease. She developed the mouse model of autoimmune uveitis, now in use worldwide. Her studies have elucidated many basic mechanisms of pathogenesis and helped to devise clinically relevant immunotherapeutic approaches. Her recent work emphasizes the Th17 response and the effects of the commensal microbiome on anti-retinal autoimmunity as well as on mucosal immunity and host defense at the ocular surface. She serves on journal Editorial Boards and is an organizer of ocular and general immunology conferences. Dr. Caspi is the recipient of the highly prestigious Friedenwald award and the Alcon Research Institute award, and has authored and co-authored over 240 publications.

 
Abstract: Commensa...Read More 

Commensals affect a multitude of processes, from development through metabolism, to immunity. In the eye, commensals play a dual role, depending on the context. The surface of the eye (conjunctiva) is a mucosal site exposed to the environment, but existence of a resident ocular surface microbiome is highly controversial. Although microbes can be detected on the ocular surface, this does not mean that they are resident there, or even alive. We isolated an organism from murine conjunctiva which fulfills Koch’s postulates for an ocular commensal and has functional consequences for maintenance of immune homeostasis and host defense at the ocular surface. On the other hand, gut commensals may in some situations play a deleterious role. Our data indicate that gut microbiota can activate migrating retina-specific autoreactive T cells, by a combination of antigen-specific and nonspecific mechanisms, and endow them with the ability to trigger autoimmune uveitis. Understanding the role that commensals play in different contexts may point the way to modulating them therapeutically through antibiotic, probiotic and prebiotic approaches.

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1:15
Immunogenicity Assessment for Peptides, Oligonucleotides, Antibody-Drug Conjugates, and Cell/Gene Therapy Products
 
Dan Sikkema
Dan Sikkema
Vice President Biologics
Frontage Laboratories
About Speaker: Dan Sikkema joined Frontage Laboratories as Vice President of Biologics Services in September 2016. He studied the regulation of Iron-repressible Outer Membrane Proteins of Yersinia pestis, the causative agent of bubonic plague, for 4 years at Michig... Read Full Bio 
 
 
Dan Sikkema
Dan Sikkema
Vice President Biologics
Frontage Laboratories
 
About Speaker:

Dan Sikkema joined Frontage Laboratories as Vice President of Biologics Services in September 2016. He studied the regulation of Iron-repressible Outer Membrane Proteins of Yersinia pestis, the causative agent of bubonic plague, for 4 years at Michigan State University earning his Ph.D. in Microbiology and Public Health. Between finishing at Michigan State University and starting at Frontage Laboratories, he spent 4 years at the State University of New York at Buffalo Medical School as a post-doctoral fellow and Research Assistant Professor (Infectious Diseases) followed by positions of increasing responsibility at Bristol-Myers Squibb (4 years), W yeth (9 years), Merck (4 years), Sanofi Pasteur (2 years), and GlaxoSmithKline (6 years). In his career, he has published 30 peer-reviewed papers and made more than 70 public presentations globally in the fields of vaccines, biologics and bioanalytical assessment, public policy, immunogenicity, and infectious diseases, working extensively with W orld Health Organization (W HO), US Centers for Disease Control (CDC), National Institute for Biological Standards and Controls (NIBSC), US FDA, and EMA as an invited participant or advisory expert. From 2012 to 2016 he led the Innovative Medicines Initiative ABIRISK project (www.abirisk.eu) to further understand the underlying mechanisms and basic biology around induction of immunogenicity to biologic drugs and th eir clinical relevance, a 5 year initiative funded at 35M Euro. July 1, 2016, he assumed the Chair position for Division V (Clinical and Diagnostic Immunology) at American Society for Microbiology, one of the world’s largest scientific organizations.

 
Abstract: New classes of biotherapeutics contin...Read More 

New classes of biotherapeutics continue to enter clinical development, each presenting new challenges for the assessment of immunogenicity. Given that the half-life of the administered product may range from very short/hours, (e.g. peptides or oligos) all the way to constituitively expressing a new gene product, the consequences of immunogenicity may also present profoundly different safety outcomes. This talk will focus on unique approaches to study peptides, oligonucleotides, antibody-drug conjugates, and most recent advances in Cell and Gene Therapy. Examples of labeling techniques for peptides, such that epitopes are not masked by he $abe0ing of the peptide, will be discussed, as well as approaches to understand the immunogenicity of Cell and Gene therapy treatments (vector neutralization, gene product, etc).

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1:40
Immunogenicity Assessment: Perspective from a Routine Clinical Laboratory
 
Melissa Snyder
Melissa R. Snyder
Consultant
Mayo Clinic
About Speaker: Melissa Snyder, PhD, DABCC is Co-Director of the Antibody Immunology Laboratory at the Mayo Clinic in Rochester, Minnesota, with an academic appointment as Assistant Professor of Laboratory Medicine and Pathology. She is board-certified in Clinical C... Read Full Bio 
 
 
Melissa Snyder
Melissa R. Snyder
Consultant
Mayo Clinic
 
About Speaker:

Melissa Snyder, PhD, DABCC is Co-Director of the Antibody Immunology Laboratory at the Mayo Clinic in Rochester, Minnesota, with an academic appointment as Assistant Professor of Laboratory Medicine and Pathology. She is board-certified in Clinical Chemistry by the American Board of Clinical Chemistry and is a member of the American Association for Clinical Chemistry, the Association of Medical Laboratory Immunologists, and the National Academy of Clinical Biochemistry.

The Antibody Immunology Laboratory is a CLIA-certified and CAP-accredited clinical laboratory which performs testing in support of patients with a variety of autoimmune diseases in many clinical specialties, including rheumatologic, hematologic, and gastrointestinal. For many of these conditions, treatment with therapeutic monoclonal antibodies is becoming standard of care. In some cases, monitoring the antibody drug concentration and assessing for anti-drug antibodies is useful for long-term patient management. The goal of the Antibody Immunology Laboratory is to develop and validate robust assays for drug quantitation and anti-drug antibody assessment, and to understand the clinical relevance of this testing.

 
Abstract: Assessme...Read More 

Assessment of immunogenicity, along with drug quantitation, is increasingly becoming the standard of care for patients being treated with monoclonal antibody therapeutics, particularly for evaluation of loss of response. More and more clinical laboratories are implementing clinical assays for this purpose. However, there are many issues that must be addressed, including assay standardization, potential drug interference, and the availability of biosimilars. This presentation will provide an overview of how clinical laboratories are dealing with these challenges in order to optimize management for patients receiving treatment with a monoclonal antibody.

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2:05
Recommendations from the AAPS Biosimilars Committee for the Validation Of Bioanalytical Methods in Support of Biosimilar Drug Development
 
Todd  Lester
Todd Lester
Principal Scientist
BioAgilytix Labs
About Speaker: Todd Lester, PMP, Bioanalytical Project Manager for BioAgilytix, oversees and leads all technical aspects of BioAgilytix’s bioanalytical studies including design, interpretation, analysis, documentation, and reporting of results, investigations, an... Read Full Bio 
 
 
Todd  Lester
Todd Lester
Principal Scientist
BioAgilytix Labs
 
About Speaker: Todd Lester, PMP, Bioanalytical Project Manager for BioAgilytix, oversees and leads all technical aspects of BioAgilytix’s bioanalytical studies including design, interpretation, analysis, documentation, and reporting of results, investigations, and deviations. A seasoned Biotech / Pharmaceutical Project Management ProfessionTodd Lester, PMP, Bioanalytical Project Manager for BioAgilytix, oversees and leads all technical aspects of BioAgilytix’s bioanalytical studies including design, interpretation, analysis, documentation, and reporting of results, investigations, and deviations. A seasoned Biotech / Pharmaceutical Project Management Professional with broad GxP expertise, Mr. Lester is well-versed in the regulations and filing requirements for FDA and EMA, particularly regarding immunogenicity assessment strategy and data interpretation. Mr. Lester holds a B.S. in Biological Sciences from Cornell University and is a licensed Project Management Professional (PMP) with the Project Management Institute (PMI).”al with broad GxP expertise, Mr. Lester is well-versed in the regulations and filing requirements for FDA and EMA, particularly regarding immunogenicity assessment strategy and data interpretation. Mr. Lester holds a B.S. in Biological Sciences from Cornell University and is a licensed Project Management Professional (PMP) with the Project Management Institute (PMI).
 
Abstract: When dev...Read More 

When developing biosimilar drugs, it is critical to demonstrate similarity to the originator drug, including similarity of physical and chemical properties as well as bioanalytical and functional analyses. This session will present the bioanalytical challenges to similarity studies for biosimilar drug development with a focus on using Neutralization Antibody Assays (NAb) to reduce the risks.

Demonstrating that a biosimilar candidate is ‘similar’ to the reference product is not trivial. One of the most frequently asked questions is ‘how similar is similar enough?’ The European Medicines Agency as well as the FDA have recognized that a biosimilar might present differences to the original branded version of the product. However, it must be demonstrated that any differences observed during the physiochemical characterization of the biosimilar candidate do not result in meaningful biological or clinical differences in the performance of the candidate to ensure safety and efficacy.

This session will summarize the recommendations of the AAPS Biosimilars Focus group and LBA Action Program Committee on the Development and Validation of PK, Anti-Drug Antibody (ADA), and Neutralization Antibody Assays (NAb) for Biosimilar Drug Development. The PK information was originally published and adopted in the white paper “Systematic Verification of Bioanalytical Similarity Between a Biosimilar and a Reference Biotherapeutic: Committee Recommendations for the Development and Validation of a Single Ligand-Binding Assay to Support Pharmacokinetic Assessments”. Discussion will expand on the original white paper and will focus ADA and in particular on how NAb assays can be used to reduce the risks to biosimilar drug development.

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2:05
Tipping the Balance: Overriding Phosphatidylserine-mediated Tumor Immune Suppression to Enhance Immune Checkpoint Therapies
 
Bruce  Freimark
Bruce Freimark
Research Director, Preclinical Oncology
Peregrine
About Speaker: Bruce Freimark, Ph.D., is currently Research Director, Preclinical Oncology for Peregrine Pharmaceuticals, which is focusing technology involving immune-oncology therapeutics targeting the membrane lipid phosphatidylserine. Previous to Peregrine he h... Read Full Bio 
 
 
Bruce  Freimark
Bruce Freimark
Research Director, Preclinical Oncology
Peregrine
 
About Speaker:

Bruce Freimark, Ph.D., is currently Research Director, Preclinical Oncology for Peregrine Pharmaceuticals, which is focusing technology involving immune-oncology therapeutics targeting the membrane lipid phosphatidylserine. Previous to Peregrine he has held management positions in the pharmaceutical and biotechnology industry in the areas of cancer and inflammation at CancerVax, Nexell Therapeutics, Valentis and Dupont-Merck. Dr. Freimark received his Ph.D. in Pathology at SUNY/Buffalo and post-doctoral training at Scripps Clinic and Research Foundation, La Jolla, CA

 
Abstract: Phosphat...Read More 

Phosphatidylserine (PS) exposure in tumors induces non-inflammatory signals via multiple specific receptors for PS on tumors and immune cells, which contribute to immunosuppression in the tumor microenvironment. Antibody blockade of PS engages with innate immune responses and activates adaptive immune responses by promoting M1 macrophages, maturation of dendritic cells and tumor specific T-cell responses. Combinations of PS with CTLA-4, PD-1 and LAG-3 immune checkpoint antibodies have been shown to induce high levels of tumor regression and long-term anti-tumor immunity in models of breast and melanoma. These immune responses correlate with an overall increase in TILs, including CD8+ T cells with a reduction in suppressive Tregs and MDSCs, and tumor gene expression signatures indicating enhanced antigen presentation. Overall, PS blockade can complement immune checkpoint therapy by promoting a localized anti-tumor response and represents a promising strategy to enhance cancer immunotherapy.

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2:05
Conference Concludes
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2:30
Afternoon Networking Break
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3:00
An Integrated Approach to Managing Immunogenicity Risk and Drug Immune Modulation
 
Emilee Knowlton
Emilee Knowlton
Immunology Sales Specialist
ProImmune Inc.
About Speaker: Emilee gained her DPhil in Infectious Diseases and Microbiology from the University of Pittsburgh under the direction of Prof. Charles Rinaldo, identifying immune responses to lytic infection with Human Herpes Virus-8. She joined ProImmune in 2013 af... Read Full Bio 
 
 
Emilee Knowlton
Emilee Knowlton
Immunology Sales Specialist
ProImmune Inc.
 
About Speaker:

Emilee gained her DPhil in Infectious Diseases and Microbiology from the University of Pittsburgh under the direction of Prof. Charles Rinaldo, identifying immune responses to lytic infection with Human Herpes Virus-8. She joined ProImmune in 2013 after completing her Post Doc in Rinaldo’s lab. She works on the ProImmune team providing innovative solutions for clients that radically improve our understanding of both desired and unwanted immune responses.

 
Abstract: Immunoge...Read More 

Immunogenicity is one of the most complex issues to address in drug design and development. Integrated platforms such as, Mass Spectrometry antigen presentation assays; DC-T and T cell proliferation assays for biologic lead selection/optimization; HLA-peptide binding assays to characterize individual epitopes and undiluted whole blood cytokine storm assays, can be used to mitigate immunogenicity risk and characterize immune responses directed toward biologics.

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Immunotherapeutics & Immunomonitoring 2017
Combination Immunotherapy (Cont’d)
Bruce Freimark, Peregrine
3:00
T-Cell Retargeting Bispecific Antibodies Generated by the Duobody Technology
 
Paul  Parren
Paul Parren
SVP & Scientific Director
Genmab
About Speaker: Prof. Paul Parren holds a PhD in molecular immunology from the University of Amsterdam (1992). He was an Associate Professor at The Scripps Research Institute in La Jolla, California, where he studied human antibodies in protection and vaccines again... Read Full Bio 
 
 
Paul  Parren
Paul Parren
SVP & Scientific Director
Genmab
 
About Speaker:

Prof. Paul Parren holds a PhD in molecular immunology from the University of Amsterdam (1992). He was an Associate Professor at The Scripps Research Institute in La Jolla, California, where he studied human antibodies in protection and vaccines again st viral infections. In 2002, he joined Genmab where he serves in the position of Senior Vice President and Scientific Director. He heads the R&D center in Utrecht where he leads an international group of about 140 employees responsible for non-clinical development and Research focusing on the development of novel antibody therapeutics for cancer. He is also a full Professor of Molecular Immunology at the Leiden University Medical Center.

Prof. Parren is an expert in translational science, biotechnology and drug development and he is dedicated to translate antibody biology and immunotherapy knowledge into innovative antibody therapeutics and technologies. He is an inventor and developer of the FDA/EMA-approved therapeutic antibodies ofatumumab (Arzerra) and daratumumab (DARZALEX), and the DuoBody and HexaBody technologies that enable the development of bispecific and effector-function enhanced antibodies. He developed 7 further clinical stage therapeutic antibodies at Genmab and with partners. He works diligently on progressing G enmab’s pipeline comprising diverse antibody formats aimed at generating innovative antibody products

 
Abstract: The DuoB...Read More 

The DuoBody® platform is rapidly becoming the method-of-choice for the discovery and development of bispecific antibodies. This platform is based on the convenient post-production method of controlled Fab-arm exchange which yields bispecific antibodies that retain the time-honored molecular structure and quality attributes of therapeutic IgGs. The DuoBody technology allows for randomized library generation and screening of large antibody panels in final format. The process is proven to be highly robust with linear scalability from bench to manufacturing scale.

To facilitate the investigation of dual-targeting concepts in immuno-competent animals and disease models, we recently developed a method for the generation of murine bsAbs using Duobody technology. (Surrogate) mouse and rat bsAbs are therefore readily generated for pre-clinical evaluation and proof-of-concept studies in rodents

Bispecific T-cell redirecting antibodies represent as a promising therapeutic approach for the treatment of cancer. The generation of bsAb with a potent ability to induce T-cell dependent tumor cell killing and their molecular characteristics will be discussed.

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3:25
Native-Format Bispecific Antibody Triggering T-cell Killing of B-Cells
 
Adelekan Oyejide
Adelekan Oyejide
Senior Director and Head of Pathology
Regeneron Pharmaceuticals
About Speaker: Adelekan Oyejide completed Veterinary School at the University of Ibadan Nigeria, and then attended the University of California, Davis for residency/PhD training in Pathology. His PhD degree in Comparative Pathology was followed by a National Resear... Read Full Bio 
 
 
Adelekan Oyejide
Adelekan Oyejide
Senior Director and Head of Pathology
Regeneron Pharmaceuticals
 
About Speaker:

Adelekan Oyejide completed Veterinary School at the University of Ibadan Nigeria, and then attended the University of California, Davis for residency/PhD training in Pathology. His PhD degree in Comparative Pathology was followed by a National Research Council Fellowship in Experimental Pathology at the Walter Reed Army Institute of Research.After a stint in academia, and following his board certification in Anatomic Pathology, Dr. Oyejide moved to the pharmaceutical industry and worked as a toxicologic pathologist for several years at Allergan and Schering Plough/Merck. He moved to Regeneron in 2012 as founding Head of Pathology within the Drug Safety and Pharmacometrics Division. Currently, as Senior Director, he leads a group of board certified pathologists with responsibility for evaluating the safety of Regeneron’s slate of biotherapeutic molecules by characterizing and interpreting microscopic tissue responses to these molecules in efficacy and toxicology studies. In collaboration with toxicologists and other Regeneron colleagues, his group is also focused on elucidating the immunopathological potentials of anti-cancer, anti-inflammatory and anti-infective monoclonal antibodies, with the ultimate aim to predict their translational significance and help nominate into drug development, the safest candidate molecules from Regeneron’s R&D pipeline.

 
Abstract: Bispecif...Read More 

Bispecific antibodies, while showing great therapeutic potential, pose formidable challenges with respect to their assembly, stability, immunogenicity, and pharmacodynamics. In this presentation, the preclinical mouse and non-human primate models used to inform development of a novel class of bispecific antibodies with native human immunoglobulin format will be described

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3:25
Bispecific Antibodies for T Cell Recruitment and Dual Checkpoint Blockade
 
John Desjarlais
John R Desjarlais
Senior Vice President, Research and Chief Scientific Officer
Xencor
About Speaker: Dr. Desjarlais is the Senior Vice President, Research and Chief Scientific Officer at Xencor, Inc. Since joining Xencor in 2001, Dr. Desjarlais has overseen the company’s engineering work on antibodies and other proteins. W ith his coworkers, Dr. D... Read Full Bio 
 
 
John Desjarlais
John R Desjarlais
Senior Vice President, Research and Chief Scientific Officer
Xencor
 
About Speaker:

Dr. Desjarlais is the Senior Vice President, Research and Chief Scientific Officer at Xencor, Inc. Since joining Xencor in 2001, Dr. Desjarlais has overseen the company’s engineering work on antibodies and other proteins. W ith his coworkers, Dr. Desjarlais has developed several novel technologies for the optimization of antibodies and other proteins, including a platform for generati on of bispecific antibodies, and has led the discovery of multiple novel antibody drug candidates for treatment of a variety of diseases. Dr. Desjarlais manages all of Xencor’s research activities, from project conception and candidate generation through preclinical proof of concept and early development. Prior to Xencor, Dr. Desjarlais was an Assistant Professor of Chemistry at Penn State University (1997-2001), where he developed and tested methods for the de novo design of protein sequences. He began his work in the field of protein design as a Jane Coffin Childs Fellow at U.C. Berkeley. Dr. Desjarlais holds a Ph.D. in Biophysics from the Johns Hopkins University and a B.S. degree in Physics from the University of Massachusetts, Amherst.

 
Abstract: Xencor h...Read More 

Xencor has applied its state of the art bispecific antibody platform to create multiple modalities for treating various cancer. CD3 bispecifics created against multiple targets, including CD123, CD20, PSMA, and SSTR2, exhibit potent in vivo pharmacology. Alternatively, building on the high activity of checkpoint combinations, we have developed a series of dual checkpoint bispecifics, including PD1 x CTLA4, PD1 x LAG3, and CTLA4 x LAG3. All of these promote strong T cell activation in vitro and in vivo.

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3:50
qPACC Enables Monitoring Cellular Immunotoxicity and Immunogenicity from 250ul Whole Blood
 
Thomas  Kleen
Thomas Kleen
Executive Vice President, Immune Monitoring
Epiontis
About Speaker: Dr. Kleen is currently Executive VP Immune Monitoring at Epiontis.  Prior he held the position of Director, Business and Technology Development and the function of Director, Assay Development and R&D at CTL, USA He received his Ph.D. in Biology ... Read Full Bio 
 
 
Thomas  Kleen
Thomas Kleen
Executive Vice President, Immune Monitoring
Epiontis
 
About Speaker:

Dr. Kleen is currently Executive VP Immune Monitoring at Epiontis.  Prior he held the position of Director, Business and Technology Development and the function of Director, Assay Development and R&D at CTL, USA He received his Ph.D. in Biology with specialty in Immunology and Virology from the Bayerische Julius-Maximilians-University Würzburg, Bavaria, Germany.  During his studies at Case Western Reserve University in Cleveland, Ohio, he investigated conditions of the human immune system affected by infectious diseases, and in particular the detailed monitoring of immune cell function in patients with human immune deficiency virus (HIV) infections.  He further conducted research on the facilitation of umbilical cord blood stem cell transplantation for immune reconstitution of adult patients with life-threatening hematologic al disorders and malignancies after treatment with full myelo-ablative regimens (http://www.linkedin.com/in/thomasokleen).

His expertise is in the areas of immunology, vaccine and biologic evaluation, immunogenicity and oncology.  One focus is monitoring of Cell Mediated Immunity (CMI) and Bio-markers during immunotherapy, vaccine development and detection of adverse immune reactions during drug development.  He spends significant time educating pharmaceutical entities and governmental agencies about validated, standardized, GLP compliant technologies, which can be deployed today during pre-clinical and clinical trials, for sample logistics and immune monitoring.
Since 2009 Dr. Kleen is member of the SITC-FDA Task Force on Immunotherapy Biomarkers, which focuses on the unique issues related to immunologic monitoring assays as well as novel methodologies for assessing the immune landscape in cancer.

 
Abstract: Novel te...Read More 

Novel technologies like qPCR-Assisted Cell Counting (qPACC) facilitate monitoring of cell mediated Immunity (CMI) directly from whole blood, greatly reduce sample amounts needed and provide for easy logistics. This allows to include routine monitoring of cellular Immunotoxicity and Immunogenicity in larger, later studies and multi-center clinical trials.

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3:50
Combination Immunotherapy: Cancer Vaccines plus an NK Driver Induces Immunologic Responses and has Overall Survival Benefit
 
Frank Jones
Frank R Jones
President and Chief Scientific Officer
Etubics Corporation
About Speaker: Dr. Jones, a founder of Etubics Corporation, is a seasoned bio-tech entrepreneur and scientist. As the founder of Etubics, Dr. Jones has served as the Company’s Chairman of the Board of Directors, Chief Executive Officer and Chief Scientific Office... Read Full Bio 
 
 
Frank Jones
Frank R Jones
President and Chief Scientific Officer
Etubics Corporation
 
About Speaker:

Dr. Jones, a founder of Etubics Corporation, is a seasoned bio-tech entrepreneur and scientist. As the founder of Etubics, Dr. Jones has served as the Company’s Chairman of the Board of Directors, Chief Executive Officer and Chief Scientific Officer since its inception. He is the Principle Investigator on many of the company’s National Institute of Health grants and contracts, which total over $20 million. He also designs and directs the clinical programs for the Company and led the “first in man” clinical trial using the Company’s Adenovirus vector platform. From 1981 to 1996, Dr. Jones served as Founding Chairman and Chief Executive Officer of the publicly traded medical device company, IMRÉ CORPORATION (now Cypress Biosciences), which focused on immunoadsorption treatments for various human diseases. From 1996 to 1998, Dr. Jones was Chairman and Chief Executive Officer of Scius Corporation, a private computer technology company which developed applications to manage and operate stirred tank manufacturing products. From 1998 to 2003 he consulted to the biotechnology industry and was the Managing Partner of Haidas Ranches, LLC a family-owned land development company. From 1983 until 1986, Dr. Jones was Director of the Immune Response Program of the Pacific Northwest Research Foundation in Seattle. He was a Researcher in the Department of Complement and Effector Biology at Memorial Sloan Kettering Cancer Center (“MSKCC”) in New York City from 1980 to 1981 and was a Research Associate in the Laboratory of Veterinary Oncology at MSKCC from 1981 to 1983. Dr. Jones is member of the American Society of Clinical Oncology, American Association for Cancer Research and the Society for Immunotherapy of Cancer. He holds a Ph.D. degree from the University of W ashington in Biological Structure/Cellular Immunology. He has 12 patents to his name and has published over 50 peer reviewed scientific papers. He has presented various business and scientific presentation s on a national and international basis

 
Abstract: The stag...Read More 

The stage has been set through advanced technology to implement multi-modal immunotherapy in such a manner so as to induce innate and adaptive immune responses and amplify those responses by suppressing immune checkpoints. We are working toward pathways to induce T-cell responses against tumor associated antigens and tumor neoepitopes while inducing natural killer (NK) cell immunity. It is important to induce innate and acquired immunity but imperative that one can “boost” those immunologic arms over time. Vectored delivery of tumor associated genes into dendritic cells has merit; however, this usually mounts an immune rejection of the delivery vector and mitigates boosting the response. We believe that we have a solution to this challenge: an Ad5 vector which is extensively gene detected in such a way that it is “stealth” to immune recognition. Therefore, we can deliver a TAA on neoepitopes gene to drive CMI and antibody production then “boost” that response by serial immunizations. As for the induction of innate (NK) response we can deliver an IL-15 superagonist (ALT-803) serially as well. Together we have shown enhanced tumor killing and induction of CMI and antibody production in murine models and are now advancing to clinical trials with these combinations.

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4:15
Conference Concludes
4:15
Effective Combination of Innate and Adaptive Immunotherapeutic Approaches in a Mouse Melanoma Model
 
Alexander  Rakhmilevich
Alexander Rakhmilevich
Distinguished Scientist
University of Wisconsin-Madison
About Speaker: Dr. Rakhmilevich is a distinguished scientist at the University of W isconsin-Madison. He obtained his MD and PhD degrees in Soviet Union. He has been working in the field of cancer immunology since 1985. His current laboratory research involves the ... Read Full Bio 
 
 
Alexander  Rakhmilevich
Alexander Rakhmilevich
Distinguished Scientist
University of Wisconsin-Madison
 
About Speaker:

Dr. Rakhmilevich is a distinguished scientist at the University of W isconsin-Madison. He obtained his MD and PhD degrees in Soviet Union. He has been working in the field of cancer immunology since 1985. His current laboratory research involves the develop ment of cancer immunotherapies using activation of macrophages via CD40 ligation

 
Abstract: Most can...Read More 

Most cancer immunotherapies include activation of either innate or adaptive immune responses. W e hypothesized that the combined activation of both innate and adaptive immunity will result in better antitumor efficacy. W e have previously shown t he synergy of an agonistic anti-CD40 monoclonal antibody (anti-CD40) and CpG-ODN in activating macrophages to induce tumor cell killing in mice. Separately, we have shown that a direct intratumoral injection of immunocytokine (IC), an anti-GD2 antibody linked to interleukin-2, can activate T and NK cells resulting in antitumor effects. W e hypothesized that activation of macrophages with anti-CD40/CpG, and NK cells with IC, would cause innate tumor destruction, leading to increased presentation of tumor antigens and adaptive T cell activation; the latter could be further augmented by anti-CTLA-4 antibody to achieve tumor eradication and immunological memory. Using the mouse GD2+ B78 melanoma model, we show that anti-CD40/CpG treatment led to upregulation of T cell activation markers in draining lymph nodes. Anti-CD40/CpG + IC/anti-CTLA-4 synergistically induced regression of advanced subcutaneous tumors, resulting in cure of some mice and development of immunological memory against B78 and wild type B16 tumors. W hile the antitumor effect of anti-CD40/CpG did not require T cells, the antitumor effect of IC/anti-CTLA-4 was dependent on T cells. The combined treatment with anti-CD40/CpG + IC/anti-CTLA-4 resulted in the increase of CD4 and CD8 cells and decrease of T regulatory cells in the tumor microenvironment. This combined therapy was also effective against distant solid tumors and lung metastases. W e suggest that a combination of anti-CD40/CpG and IC/anti-CTLA-4 should be developed for clinical testing as a potentially effective novel immunotherapy strategy.

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