Cambridge Healthtech Institute’s 13th Annual

Immunology for Biotherapeutics

Understanding and Manipulating the Immune System for Therapeutic Advantage

October 19, 2021 ALL TIMES 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.

9:00 am Registration and Morning Coffee


9:30 am

Chairperson's Opening Remarks

Ethan Shevach, MD, Senior Investigator, Cellular Immunology, Laboratory of Immune System Biology, NIH NIAID

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.

10:10 am

Antigen Processing and Presentation: The Basis of T Cell Activation

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.

10:40 am

The Role of the Innate Immune System and Implications for Biotherapeutics

Han-Yu Shih, PhD, Investigator, NeuroImmune Regulome, NIH NEI

The field of innate lymphoid cell (ILC) biology has progressed rapidly, with appreciation of these cells’ role in immunity, barrier tissue integrity, and homeostasis. 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 the development of new strategies to treat autoimmunity, infection, and cancer.

11:10 am Session Break
11:30 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.


12:00 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.

1:00 pm Enjoy Lunch on Your Own


2:20 pm

Bispecific Technology to Leverage Immune Responses for Treatment of Cancer

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 bispecific approaches including dual checkpoint blockade and tumor anchored co-stimulation are also being developed to enhance cancer therapy. These approaches will be summarized in the context of molecule design and target selection.

2:50 pm

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.

3:20 pm

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 diverse class of therapeutics, 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 overview, 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.


Harnessing the Immune System for Biotherapeutics

Panel Moderator:
Daron Forman, PhD, Principal Scientist, Discovery Biotherapeutics, Bristol-Myers Squibb
Paul Moore, PhD, Vice President, Cell Biology & Immunology, MacroGenics, Inc.
Bonnie Rup, PhD, Biotechnology Consultant, Bonnie Rup Consulting
Simone Nicholson, PhD, Discovery Safety Specialist, AstraZeneca
5:10 pm Close of Symposium