TS1: Immunology for Biotherapeutics

This 1.5-day lecture-based seminar led by experts in their fields will examine the roles of the various cells involved in the immune response and how they can be manipulated and harnessed for therapeutic purposes. Attendees will learn about the importance of T cells, how they are activated, and their role in immune regulation. The course will include immunotherapy particularly for oncology, such as the exciting advances in controlling checkpoint inhibitors, and application of adoptive T cell therapy such as CAR-Ts. Safety aspects of manipulating the immune response will be emphasized and examples of what can go wrong will be provided. Current developments with vaccines will be covered and we will examine the impact of immunogenicity on safety and efficacy of biotherapeutics.

Who should attend: Scientists and academics in all aspects of drug discovery and development, including biotherapeutic engineering, drug development, analytical sciences, bioproduction, and preclinical, translational and clinical studies, oncology and gene therapy.

Tuesday, October 24

7:30am Registration and Morning Coffee

8:25 Chairperson’s Opening Remarks

8:30 Introduction to Immunology for Biotherapeutics and the Role of T Regulatory Cells

Ethan Shevach, M.D., Senior Investigator, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH

The major role of the immune system is to provide protective responses to pathogenic microorganisms. The immune system consists of several distinct cell types and each type plays a unique role. Dysregulation of the immune system can result responses against self-antigens and in the development of autoimmune diseases. A specialized subset of T lymphocytes, termed T regulatory (Treg) cells, functions to suppress anti-self responses. Modulation of Treg function with drugs or biologics represents a major approach to the treatment of autoimmune disease.

9:30 Antigen Processing and Presentation: the Basis of T Cell Activation

David H. Margulies, M.D., Ph.D., Chief, Molecular Biology, Laboratory of Immunology Lab, NIAID, National Institutes of Health

Antigen Presenting Cells process protein antigens into peptides for binding by either Major Histocompatibility Class I (MHC-I) or Class II (MHC-II) molecules which are then displayed at the cell surface as peptide/MHC complexes where they are recognized by T cell receptors leading to T cell activation. Cell biological, biochemical, and structural details of these processes as we now understand them will be discussed.

10:30 Coffee Break in the Exhibit Hall

11:00 Applying Bispecific Technology to Modulate the Immune Response for Therapeutic Intervention

Paul Moore, Vice President, Immunology and Cell Biology, Macrogenics, Inc.

Bispecific antibody based molecules afford therapeutic opportunities not feasible with single-target antibodies or combinations. The most advanced clinical strategy in oncology exploits the ability of bispecific molecules to co-engage T-cells with tumor cells resulting in tumor cell lysis and T-cell expansion. Additional approaches to leverage immune cells through bispecific targeting are being explored in oncology, autoimmunity and infectious diseases. These approaches will be summarized in the context of molecule design and target selection.

12:00pm Immunology Safety Considerations for Biotherapeutics

Rakesh Dixit, Ph.D., Vice President, R&D, Global Head, Biologics Safety Assessment, MedImmune, Inc.

In this presentation, I shall examine the challenges of biotherapeutics impacting on the immune response, and the challenges investigators face managing, dose, scheduling, and satisfying the regulatory requirements. The checkpoint inhibitors used for immunotherapy have a natural role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. Immunotherapies in general, and technologies modifying T cell function and those involving cytokines present dangers of autoimmune disease, cardiovascular disorders, and additional challenges, especially when used in combination.

1:00 Lunch

2:30 Biopharmaceutical Product Immunogenicity: What Causes It and What are the Safety and Efficacy Consequences?

Bonita (Bonnie) Rup, Ph.D., Biopharmaceutical Consultant, Bonnie Rup Consulting

Biopharmaceuticals represent a rapidly growing class of therapeutic product, contributing significantly to advancing treatment of serious diseases including chronic inflammatory and autoimmune diseases, genetic deficiencies, and cancer. Unfortunately, unwanted immunogenic responses against some of these products can occur, often reducing efficacy and sometimes causing safety consequences such as hypersensitivity, immune complex disease, and autoimmune syndromes. In this talk, factors that affect the degree to which the immune system responds and the degree to which the response affects the efficacy and safety of the biopharmaceutical in patients are discussed.

3:45 Refreshment Break in the Exhibit Hall

4:15 Vaccines: Understanding the Mode of Action, Progress to Date, and On-Going Challenges

Michael Lacy, Ph.D., Lead Scientist, Non-Clinical Development, Emergent BioSolutions

Complex immune responses result from the complexity of whole pathogen vaccines. Vaccines can be simplified to 3 general components, each of which is supplied by whole pathogens in a convenient package. Despite complex immunity within the recipient, measurements are limited usually to net immunity assessments. Emerging safety issues may lead to purified and quantified vaccine components. Purified immune stimulants that mimic native stimulants may be effective. Formulations may preserve epitopes and control unwanted immunity. Selection of conserved epitopes may bypass rapid mutational rates of pathogens.

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:30 End of Day One of Immunology for Biotherapeutics

Wednesday, October 25

8:00 am Morning Coffee

8:25 Chairperson’s Remarks

8:30 Immuno-Oncology Part One: Harnessing the Body’s Natural Immune Response to Fight Cancer

Jochem Gokemeijer, Ph.D., Associate Director, Molecular Discovery Technology, Bristol-Myers Squibb

Checkpoint inhibitor as cancer treatment have shown remarkable response rates in previously hard to treat cancers by redirecting the body’s own immune system to recognize and eliminate tumor cells.

Here we will discuss the current state of I-O agents in the clinic, challenges related to toxicities, biomarker approaches for patient stratification and future directions of the field.

9:30 Immuno-Oncology Part Two: Adoptive T Cell Therapy

J. Joseph (Jos) Melenhorst, Ph.D., Director, Product Development & Correlative Sciences, Center for Cellular Immunotherapies, University of Pennsylvania

The early realization that cancer patients may exhibit tumor-resident or circulating T cells that respond to the tumor has led to a flood of basic and translational studies aimed at characterizing the antigens recognized by T cells and the T cell receptor (TCR) chains responsible for this tumor specificity. Via rapid developments in gene engineering such receptors have been utilized in pre-clinical and even clinical studies to target tumor cells. In some cases, the native antigen affinity was altered to boost tumor reactivity, which sometimes led to the desired effect, occasionally with deleterious consequences. Similar biotechnological developments, fueled by discoveries in basic immunology, have led to the introduction of man-made tumor-targeting receptors made up of B cell and T cell domains, currently known as chimeric antigen receptors or CARs. In my two-part talk I will discuss the evolving field of adoptive T cell therapy, and compare and contrast tumor targeting efforts with allogeneic, autologous minimally manipulated to the TCR and CAR-redirected T cells. Topics to discuss are safety, efficacy, toxicity; clinical trials in hematologic and solid tumors, and future directions to enhance immunogene therapy of cancer.

10:30 Break

11:00 Immuno-Oncology Part Two: Adoptive T Cell Therapy (continued)

J. Joseph (Jos) Melenhorst, Ph.D., Director, Product Development & Correlative Sciences, Center for Cellular Immunotherapies, University of Pennsylvania

12:00 Discussion

12:10 End of Immunology for Biotherapeutics

Instructor Biographies

Ethan Shevach, M.D., Senior Investigator, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH

Dr. Shevach received his A.B. and M.D. degrees from Boston University. He is presently Chief, Cellular Immunology Section, Laboratory of Immunology. Dr. Shevach is the author of over 450 papers in the field of Immunology and his research interests over the years have included antigen presentation and processing, T lymphocyte activation, pathogenesis of autoimmunity, and most recently the role of regulatory T cells in immune responses. He served as Editor-in-Chief of the Journal of Immunology from 1987 to 1992 and as Editor-in-Chief of Cellular Immunology from 1996 to 2007. He is a member of the editorial boards of several journals including Immunity, Journal of Experimental Medicine, and Human Immunology.

Bonita (Bonnie) Rup, Ph.D., Biopharmaceutical Consultant, Bonnie Rup Consulting

Bonita Rup is a biopharmaceutical development consultant, providing expert advice on bioanalysis, immunogenicity risk assessment, and related regulatory strategy aspects of biopharmaceutical development. Previously she was Research Fellow at Pfizer, and lead the Immunogenicity Discipline, Assistant Vice President of Protein Bioanalytics in Wyeth, and held various positions directing development and application of immuno-ligand binding assay technologies for PK, immunogenicity and protein impurity analysis, and other aspects of biopharmaceutical development. During her career, she has been involved in multiple regulatory filings during preclinical, clinical development and marketing approval of biopharmaceutical products. She has been a member of AAPS, EIP, European IMI ABIRISK consortium, and Biosafe; with these organizations, she has been a co-author for multiple publications related to monitoring immunogenicity and bioanalysis of therapeutic proteins. Bonnie received her B.S. from University of Massachusetts, Amherst, Ph.D. from University of Texas, Austin, and conducted postdoctoral research at Duke University and University of Rochester, NY.

Paul A. Moore, Ph.D., Vice President, Immunology and Cell Biology, Research, MacroGenics, Inc.

Over 20 years of experience working in biotech, coordinating efforts focused on the discovery and development of novel biologic based therapies. Began biotechnology career at Human Genome Sciences, where directed genomic-based target discovery programs and the preclinical development of various protein and mAb-based therapeutics for the treatment of cancer, metabolic, and autoimmune diseases. Notably these efforts led to the discovery of BLyS as a B-cell survival factor providing the basis for the development of Benlysta for the treatment for lupus. At MacroGenics, leads a research group dedicated to the discovery, preclinical development and clinical translational biology of antibody-based therapeutics including Fc-optimized mAbs and bispecifics for cancer or autoimmune disease through harnessing of the host immune system. Obtained PhD from University of Glasgow and performed post-doctoral work at the Roche Institute of Molecular Biology; co-authored over 70 peer-reviewed manuscripts and 40 issued US patents.

David H. Margulies, M.D., Ph.D., Chief, Molecular Biology, Immunology Lab, NIAID, National Institutes of Health

Dr. Margulies received his AB in analytical biology from Columbia University in 1971 and his MD and PhD degrees from the Albert Einstein College of Medicine in 1978. Following training in Internal Medicine at Columbia-Presbyterian Medical Center from 1978 to 1980, he was a research fellow at the National Institutes of Health (NIH) where he studied the molecular biology of the MHC molecules. Since 1983 he has been an independent investigator in the Laboratory of Immunology at the NIAID of the NIH where his interests in MHC molecule genetics, function, and structure have expanded to understanding MHC interactions with T cell receptors and natural killer (NK) cell receptors. His current research explores the structural basis of peptide loading of MHC molecules, the role of MHC structure in drug hypersensivity, allostery in TCR signaling, and mechanisms of viral immunoevasion.

Rakesh Dixit, Ph.D., Vice President, Safety Assessment, Medimmune (A member of AstraZeneca)

Rakesh is a Vice President, R & D and the Global Head of the Biologics Safety Assessment comprising of Toxicology, Pathology and Laboratory Animal Resources functions where he is responsible for overseeing the biologics safety assessment of the entire MedImmune biologics portfolio in all therapeutics areas (2006-todate). Prior to joining MedImmune in 2006, Rakesh served as Senior Director of Toxicology in Johnson and Johnson and Associate Director-Research Fellow in Toxicology in Merck and Co., Inc. (1992-2005). Rakesh has over 25 years of experience in developing pharmaceutical and biotechnology-derived drugs and is the author of over 60 peer-reviewed scientific publications and has been invited to deliver Rakesh is regarded as a Key Opinion Leader in Toxicology community. Rakesh is the Editor-in-chief of Toxicology Mechanisms and Methods and an Associate Editor of Toxicology and Applied Pharmacology and Journal of Toxicology and Environmental Health- all key major toxicology journals.

Michael Lacy, Ph.D., Lead Scientist, Non Clinical Development, Emergent BioSolutions

Michael Lacy performed graduate work to dissect a model antibody system, then added a T cell immunology post-doc at the University of Illinois at Urbana-Champaign. Moving to corporate research, he inspected immune responses to monophosphoryl lipid A at Ribi ImmunoChem, then synthetic TLR4 agonists with Corixa Corporation, morphing to emerging diseases with Emergent BioSolutions, including new generation anthrax vaccines and therapeutics.

Jochem Gokemeijer, Ph.D., Associate Director, Molecular Discovery Technology, Bristol-Myers Squibb

Jochem has been at Bristol-Myers Squibb for 14 years in different roles of responsibility focused on biologics drug development. For the last 8 years he has been focused on building a group for preclinical immunogenicity risk assessment and mitigation. He received his training at the University of Groningen and the Dana Farber Cancer Institute.

J. Joseph (Jos) Melenhorst, Ph.D., Director, Product Development & Correlative Sciences, Center for Cellular Immunotherapies, University of Pennsylvania

After his training in translational immunology at the Leiden University Medical Center, Leiden, Netherlands, Dr. Melenhorst completed a post-doctoral position at the National Institutes of Health in Bethesda, Maryland where he continued as a staff scientist in the field of hemato-oncology. In August 2012, Dr. Melenhorst was appointed Deputy Director of Clinical Cell and Vaccine Production Facility within the Center for Cellular Immunotherapies, Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, and in October of 2013 he assumed the role of Director of the Product Development & Correlative Sciences (PDCS) laboratory. Dr. Melenhorst’s interest in translational research is continued at the PDCS lab where his work focuses on the improvement of the potency of chimeric antigen receptor-expressing T (CART) cells in certain leukemias and solid tumors, the understanding of the in vivo potency of CART cells, and biomarkers of immunotherapy. Dr. Melenhorst is a highly original scientist who has originated and contributed to innovations at the National Institutes of Health and the University of Pennsylvania.

Each CHI Training Seminar offers 1.5 Days of instruction with start and stop times for each day shown above and on the Event-at-a-Glance published in the onsite Program & Event Guide. Training Seminars will include morning and afternoon refreshment breaks, as applicable, and lunch will be provided to all registered attendees on the full day of the class.

Each person registered specifically for the training seminar will be provided with a hard copy handbook for the seminar in which they are registered. A limited number of additional handbooks will be available for other delegates who wish to attend the seminar, but after these have been distributed no additional books will be available. 

Though CHI encourages track hopping between conference programs, we ask that Training Seminars not be disturbed once they have begun. In the interest of maintaining the highest quality learning environment for Training Seminar attendees, and because Seminars are conducted differently than conference programming, we ask that attendees commit to attending the entire program, and NOT engaging in track hopping, as to not disturb the hands-on style instruction being offered to the other participants.