Senior Principal Scientist Bristol Myers Squibb Princeton, New Jersey
CAR-T-cells can drive MHC class-I-mediated CD8+ cytotoxic T-cell response towards CAR construct in addition to antibody response. Health authorities recommend testing both humoral and cellular immunogenicity toward the CAR-T protein. Assessment of humoral response can leverage the knowhow from anti-drug antibody assays for biologics. However, measuring CAR-T induced T-cell cytotoxicity is challenging due to several reasons such as cell survival, assay variability, difficulty in obtaining positive controls etc. This talk will describe the overall strategy for investigating cellular immunogenicity, risk assessments, sample collection/logistics, and design of CAR domain related peptides to elicit the memory response from dosed subjects. Preliminary results from a CAR-T-cell therapy indicates the presence of CAR-T specific CD8+ T-cells in dosed subjects against specific domains of CAR, allowing for epitope mapping and potentially inform the design of next generation constructs. The relevance/impact of the CAR-T cellular immunogenicity and its association with humoral response will also be discussed.
Learning Objectives:
Upon completion, participant will be able to discuss potential factors that can drive a cellular immune response to CAR-T-based products; bioanalytical strategy that provides relevant information to understand cellular immunogenicity