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Immunology and Immunotherapy

GTCbio | October 24th, 2017

Immunotherapy involves treatment of diseases by induction, enhancement, or suppression of an immune response. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immune cell activation and differentiation occurs concurrently with metabolic reprogramming. This ensures that activated cells generate the energy and substrates necessary to perform their specified function. Likewise, the metabolic programs among different cells of the immune system may vary. By targeting different metabolic pathways, these differences allow for selective regulation of immune responses. In recent years, immunotherapy has been a great interest to researchers, clinicians and pharmaceutical companies, particularly because of its great potential for treatment of various forms of cancers.

Over the past few years numerous Phase III trials have demonstrated immunotherapy to confer an overall survival benefit in advanced, recurrent or metastatic melanoma, non-small-cell lung cancer, renal cell cancer, head and neck cancer, transitional cell carcinoma of the bladder and prostate cancer. However despite these successes, not surprisingly, these immunotherapies show only benefit in a limited number of patients because they affect only very specific points/processes in the cancer immunity cycle. Research has shown that resistance mechanisms by tumour cells may be acquired during therapy or may be elicited by the tumour microenvironment.

The discovery of the biological functions of the interleukin-23/-17 axis has led to the identification of IL-23 and IL-17 as important participants in the pathogenesis of several immune-mediated diseases. Therapeutic agents targeting these cytokines and/or their receptors have now been developed as potential treatment strategies for common immune-mediated diseases. Furthermore, recent findings show that the microbiota plays an important role in patient responses to cancer chemotherapy and checkpoint immunotherapy. A better understanding of how individual or communities of bacteria (or commensal viruses and fungi) regulate tumor-specific T cell responses may pave the way for microbiota-based cancer therapies.

Some of the latest research has indicated that combination of immune-modulation and radiation could tip the balance of the host immune response to promote cure; primary and metastatic CRPC showed robust synergistic responses when immune checkpoint blockade was combined with MDSC-targeted therapy; combining MEK inhibition with T-cell-directed immunotherapy might lead to more durable efficacy; combined immunotherapy with NY-ESO-1-specific CAR+ T cells and an NY-ESO-1+ T-APC vaccine will lead to enhanced anti-myeloma efficacy due to improved persistence of the CAR T effector cells; lenalidomide seems to be a promising combination partner for T-cell based immunotherapy approaches in CLL patients and many more. Merck (MRK) won U.S. approval for the use of its immunotherapy Keytruda in combination with chemotherapy to treat patients newly diagnosed with non-small cell lung cancer. In addition, recent FDA approvals for CAR T therapies from Novartis and Gilead opened the door for a new era of treatment options for cancer. Furthermore, Bristol-Myers Squibb is teaming up with France’s Transgene to combine Opdivo with investigational therapeutic vaccine TG4010 in lung cancer. A new wave of therapeutic vaccine treatments for cancer is emerging, and is among the novel approaches being touted as combinations to boost results from the PD-1 drugs. Furthermore, immunotherapy is gaining ground in the treatment of allergy, multiple sclerosis, Alzheimer’s, and Type 1 Diabetes.

ITX Keynotes 2018

GTCbio’s 16th ImmunoTX Summit will be held on January 30-31, 2018 in San Diego, CA and the keynote speakers include the following:

Scott Durum, Chief, Section of Cytokines and Immunity, NIH – National Cancer Center – Center for Cancer Research

Dr. Durum’s research is aimed at determining the mechanism of action of IL-7, a cytokine that is essential for T cell development and survival. Understanding the IL-7 pathways has given insights into the physiology of lymphocytes, suggested therapeutic strategies for modulating immunity, and revealed mechanisms of leukemogenesis.

Gordon Freeman, Professor, Department of Medical Oncology, Professor of Medicine, Dana Farber Cancer Institute, Harvard University

Dr. Freeman’s research has identified the major pathways that control the immune response by inhibiting T cell activation (PD-1/PD-L1 and B7-2/CTLA-4) or stimulating T cell activation (B7-2/CD28). Principally involved in basic laboratory research, he has studied the B7-CD28 gene family, showing that B7-2/CD28 is the major costimulatory pathway for T cell activation and that PD-L1/PD-1 is the major coinhibitory pathway for T cell activation. He received 2017 Warren Alpert Foundation award for this work that led to development of PD-1 pathway blockade for cancer immunotherapy.

Michael Karin, Distinguished Professor, Department of Pharmacology, University of California, San Diego

Dr. Karin heads UC San Diego’s Laboratory of Gene Regulation and Signal Transduction and has long been interested in how cells and biological systems function at the molecular level in both healthy and stressed or diseased states. He is a renowned expert on the interaction of mammalian cells with their environment and, specifically, the role of inflammation in cancer, heart disease, diabetes and other chronic diseases. His research has broad, practical implications and applications, notably in issues like obesity and cancer.

Jennifer Towne, Senior Scientific Director, Janssen

Dr. Towne’s research focuses on the biology of IL-1 family members, primarily IL-36, IL-17 family members and IL-23 in the skin, lung and gut. She led or was a key contributor to multiple large and small molecule project teams currently in clinical development for psoriasis and inflammatory bowel disease (IBD). She is currently the discovery lead for the IBD disease area stronghold where she is responsible for discovery efforts to develop innovative therapeutics for the treatment, prevention and cure of IBD.

Please visit https://www.gtcbio.com/conferences/immunotx-summit/?section=fullagenda for a detailed agenda.  We look forward to see you at the ImmunoTX summit on Jan 30-31, 2018, at the Coronado Island Marriott Resort, San Diego, CA.