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.

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.

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.

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.

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.

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.

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.

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.

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.