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.

This presentation will overview the 4 areas of hypersensitivity: immediate-type 1-IgE-mediated, type II-antibody-dependent cytotoxicity, type III-immune-complex-mediated, and delayed-type hypersensitivity. Type 1 human allergic disease will then be examined, covering its pathophysiology, current diagnostic strategies, four modes of disease management, and special caveats relating to food, drug, venom, and respiratory allergic disease. Finally, the new discipline of molecular allergology will be highlighted with an emphasis on 10 cross-reactive allergen families and how allergenic molecules have improved the accuracy of allergy diagnosis.

Antibody based therapeutics have provided great therapeutic benefit to many patients across various disease states. Multi-specific antibodies afford therapeutic opportunities not feasible with single-target antibodies or combinations, while drug conjugates provide opportunity to extend therapeutic benefit through combining the targeting specificity of an antibody with a “payload." Examples of these advances will be summarized in the context of molecule design, target selection, biological characterization, and clinical benefit.

Biotherapeutics, which include immunotherapies, antibody-drug conjugates, gene-based and cellular therapies, are currently used in the treatment of numerous diseases. Safety concerns arise with modality and with each unique mechanism of action of the biotherapeutic. 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.

A comprehensive understanding of the drug modality, mode of action, and immunogenicity risk is crucial to evaluate the impact of a given drug on both safety and efficacy. Immunogenicity risk evaluation involves analyzing both early prediction data and late clinical data. While early prediction data can provide insight into the potential immunogenicity risk, utilizing an integrated data approach that includes not only the appropriate assays but also the correlation of pharmacokinetic (PK), pharmacodynamic (PD), and anti-drug antibody (ADA) data with clinical efficacy and safety data is essential for a more accurate assessment. In this presentation, we will provide examples of how an integrated data approach, along with a thorough understanding of the drug modality and immunogenicity risk, can explain unexpected clinical data.