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.

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.

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.

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.

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.

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 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.