HLA DR alleles of antigen presenting cells, display immunogenic peptides to T-cells, driving T-cell dependent B-cell response, leading to anti-drug antibody (ADA) responses development in patients treated with biologics. Hence, HLA-DRB alleles could serve as personalized biomarker and its individualized T-cell Epitope Measure (iTEM) can be used to quantitate patients’ immune response. In this work, observed ADA responses, and HLA-DR allele information from a protein biologic drug treated patients were systematically datamined. Findings are discussed in the context of patient’s immune response, patients' HLA-DRB1 alleles, their demographic distribution, calculated iTEM score, zygosity status, and in silico predicted immunogenic drug peptides in vitro binding affinities. This novel association analysis could help to make comprehensive patient related baseline prognostic factor which would aid in precluding patients predisposed to ADA development for that biologic. Implications of this work for future patient population selection, personalized treatment, drug testing, safety guidance, precision drug discovery and development will be discussed.
Learning Objectives:
Understand HLA associations to patients’ immunogenicity risk and their implications to future drug discovery and development, clinical regulation and patient care.
Understand current practices and methods of immunogenicity in silico prediction, large immunogenicity data set bioanalysis, and personalized treatment.
Stimulate discussion and learning on future of multiple biologic modality therapeutics from the point of immunogenicity and implications on clinical safety and efficacy related to pharmacokinetics, toxicokinetics, and adverse effects.
Upon completion, participants will be able to understand and explore how high content data analysis aids biologic discovery in the preclinical and patient selection and personalizing treatment in clinical areas.
Upon completion, participants will have the opportunity in updating and standardizing with others in the industry.
