Immunology for Biotherapeutics

Understanding and Manipulating the Immune System for Therapeutic Advantage

October 6, 2020 ALL TIMES U.S. EDT

Many of the exciting advances 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 rapidly. T and B lymphocyte subsets, innate lymphoid cells (ILCs), macrophages, dendritic cells and cytokines are all involved in a complex manner. There is the potential for manipulation for therapeutic advantage, yet the danger of 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.

Tuesday, October 6

CURRENT UNDERSTANDING OF IMMUNE MECHANISMS

9:05 am KEYNOTE PRESENTATION: Current Understanding of the Role of T Regulatory Cells and Their Modulation
Ethan Shevach, MD, Senior Investigator, Cellular Immunology, Laboratory of Immune System Biology, NIH NIAID

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.

9:25 am Antigen Processing and Presentation: T Cell Activation and Interaction between the Cells of the Immune System
Kannan Natarajan, PhD, Staff Scientist, NIH NIAID

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.

9:45 am T Helper and Innate Lymphoid Cell Subsets
Jeff Zhu, Senior Investigator, Laboratory of Immune System Biology, NIAID, NIH

CD4+ T helper (Th) lymphocyte subsets, through their production of distinct effector cytokines, play a central role in orchestrating adaptive immune responses. Innate lymphoid cell (ILC) subsets mirror Th subsets in cytokine production. Specific Th cell and ILC subsets mediate crucial functions during different types of protective immune responses to various microorganisms. Inappropriate Th responses and ILC activation to pathogens may lead to chronic infection and/or tissue damage to the host. On the other hand, aberrant Th cell and ILC activation may result in many inflammatory, allergic, or autoimmune diseases. In this talk, I will discuss the similarities and differences between Th cell and ILC subsets, and their functional crosstalk during immune responses.

10:05 am Coffee Break - View Our Virtual Exhibit Hall

HARNESSING THE IMMUNE SYSTEM FOR BIOTHERAPEUTICS

10:20 am Applying Bispecific Technology to Modulate the Immune Response for Therapeutic Intervention
Paul Moore, PhD, Vice President, Cell Biology & Immunology, 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.

10:40 am Immunology Safety Considerations for Biotherapeutics
Simone Nicholson, PhD, Discovery Safety Specialist, AstraZeneca

Biotherapeutics are currently used in the treatment of numerous diseases which encompass oncology and autoimmune inflammatory  disorders.  Safety concerns arise both with modality and with each different mechanism of action of the biotherapeutics.  Investigators are challenged to predict, monitor and mitigate if possible, potential adverse effects in patients while ensuring efficacy and satisfying the regulatory requirements for drug approval.  Examples of these safety concerns and how their challenge is met and managed are the subject of this presentation.

11:00 am Biopharmaceutical Product Immunogenicity: What Causes It and What Are the Safety and Efficacy Consequences?
Bonnie Rup, PhD, Biotechnology 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.

11:20 am PANEL DISCUSSION:

Live Q&A with Session Speakers

Panel Moderator:
Ethan Shevach, MD, Senior Investigator, Cellular Immunology, Laboratory of Immune System Biology, NIH NIAID
Panelists:
Kannan Natarajan, PhD, Staff Scientist, NIH NIAID
Jeff Zhu, Senior Investigator, Laboratory of Immune System Biology, NIAID, NIH
Paul Moore, PhD, Vice President, Cell Biology & Immunology, MacroGenics, Inc.
Simone Nicholson, PhD, Discovery Safety Specialist, AstraZeneca
Bonnie Rup, PhD, Biotechnology Consultant, Bonnie Rup Consulting
11:35 am Recommended Short Course*
SC1: Mechanism of Action and Risk-Based Approach for Developing Neutralizing Ab Assays

*Separate registration required. See short course page for details.


11:35 am Lunch Break - View Our Virtual Exhibit Hall

IMMUNO-ONCOLOGY

1:05 pm Harnessing the Body’s Natural Immune Response to Fight Cancer
Daron Forman, PhD, Principal Scientist, Discovery Biotherapeutics, Bristol-Myers Squibb

Checkpoint inhibitors have shown remarkable response rates in some 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 checkpoint inhibitors in the clinic, challenges related to toxicities, biomarker approaches for patient stratification, and future directions of the field.

1:25 pm Adoptive T Cell Therapy
Jos Melenhorst, PhD, Director, Product Development & Correlative Sciences, Center for Cellular Immunotherapies, University of Pennsylvania

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.

1:45 pm Oncolytic Viruses: Impact of the Virus on Tumor Cells, Local Microenvironment, and Systemic Adaptive Immune Response
Cheryl Pickett, MD, PhD, Associate Research Physician, Cancer Therapy Evaluation Program, Investigational Drug Branch, NIH NCI

Intratumorally injected oncolytic viruses preferentially infect, replicate, and lyse cancer cells. However, through release of tumor-specific antigens and cytokines, they also induce changes in tumor local immune microenvironment with activation of the adaptive immune system, maturation of antigen-presenting cells, subsequent activation of cytotoxic CD8 T cells, and response in non-injected lesions. These changes in immune effector cells appear to sensitize tumors to checkpoint inhibitors. We will review data on oncolytic viruses in clinical development, with particular attention to systemic responses and the potential for combination with other immunotherapy. In addition, we will review some of the unique delivery and safety issues for oncolytic viral therapy.

Basile Siewe, Director, Business Development, The Jackson Laboratory

The JAX® cytokine release syndrome evaluation study platform leverages PBMC humanized NSG™ mice to overcome limitations of in vitro assays in assessing the potential of immunotherapeutics to elicit CRS. 

2:35 pm PANEL DISCUSSION:

Live Q&A with Session Speakers

Panel Moderator:
Daron Forman, PhD, Principal Scientist, Discovery Biotherapeutics, Bristol-Myers Squibb
Panelists:
Jos Melenhorst, PhD, Director, Product Development & Correlative Sciences, Center for Cellular Immunotherapies, University of Pennsylvania
Cheryl Pickett, MD, PhD, Associate Research Physician, Cancer Therapy Evaluation Program, Investigational Drug Branch, NIH NCI
Basile Siewe, Director, Business Development, The Jackson Laboratory
2:50 pm Happy Hour - View Our Virtual Exhibit Hall
3:35 pm Close of Symposium
2:35 pm Recommended Short Course*
SC2: Overcoming Drug and Target Interference in ADA Assays

*Separate registration required. See short course page for details.







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