Cambridge Healthtech Institute’s Inaugural

Immunology for Biotherapeutics

Understanding and Manipulating the Immune System for Therapeutic Advantage

October 22, 2018

 

Many of the exciting developments in drug discovery and development today concern the immune response and its manipulation and control. Our understanding of immune involvement in therapeutic disorders and their treatment is developing all the time. T and B lymphocyte subsets, NK cells, macrophages, dendritic cells and cytokines are all involved in a complex manner, and interference with one could have disastrous consequences if not well understood. At this symposium, attendees will find out how to utilize the immune system and overcome inhibitory factors without overlooking potential safety issues.

Monday, October 22

8:30 am Registration and Morning Coffee

9:30 Chairperson’s Opening Remarks

Ethan Shevach, MD, Senior Investigator, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH


9:40 KEYNOTE PRESENTATION: Current Understanding of the Role of T Regulatory Cells and Their Modulation

Ethan Shevach, MD, 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 in 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.

10:15 Antigen Processing and Presentation: The Basis of T-Cell Activation

David H. Margulies, MD, PhD, Chief, Molecular Biology, 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.

11:00 Networking Coffee Break

11:30 Current Understanding of the Role of the Innate Immune System and Implications for Biotherapeutics

Han-Yu Shih, PhD, MS, Research Fellow, National Institute of Arthritis and Musculoskeletal and Skin Disease, (NIAMS), NIH

The field of innate lymphoid cell (ILC) biology has progressed rapidly, with appreciation of these cells’ role in immunity, barrier tissue integrity and homeostasis. ILCs can be classified based on their cytokine production profiles that mirror to the patterns in their adaptive CD4 T helper (Th) cell analogs. Unlike Th cells, ILCs respond to pathogens promptly without the need of antigen-specific receptor recognition. Understanding how ILCs differentiate and contribute to the immunoregulation in health and diseases is fundamentally important for development of new strategies to treat autoimmunity, infection and cancer.

12:15 pm Sponsored Presentation (Opportunity Available)

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

2:00 Applying Bispecific Technology to Modulate the Immune Response for Therapeutic Intervention

Paul Moore, PhD, 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.

2:45 FEATURED PRESENTATION: Immunology Safety Considerations for Biotherapeutics

Rakesh Dixit, PhD, 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.

3:30 Networking Refreshment Break

3:45 Biopharmaceutical Product Immunogenicity: What Causes It and What Are the Safety and Efficacy Consequences?

Bonita (Bonnie) Rup, PhD, 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 are discussed.

4:30 Vaccines: Understanding the Mode of Action, Progress to Date, and Ongoing Challenges

Michael Lacy, PhD, 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.

5:15 Discussion

5:30 Close of Symposium

5:30 Dinner Short Course Registration


6:15-9:15 Recommended Dinner Short Course*

SC4: Immunology for Immuno-Oncology

Part One: Harnessing the Body’s Natural Immune Response to Fight Cancer

Instructor: Jochem Gokemeijer, PhD, Associate Director, Molecular Discovery Technology, Bristol-Myers Squibb

Checkpoint inhibitors as a 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 immune-oncology agents in the clinic, challenges related to toxicities, biomarker approaches for patient stratification, and future directions of the field.

SC4: Part Two: Adoptive T Cell Therapy

Instructor:J. Joseph (Jos) Melenhorst, PhD, Director, Product Development & Correlative Sciences, 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. 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 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.

* Separate registration required.

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