Principal Scientist Navigate Biopharma Carlsbad, California
Chimeric antigen receptor T-cell (CAR-T) therapies like Tisagenlecleucel have profoundly transformed the treatment of advanced relapsed or refractory (r/r) B-cell malignancies with patients continuing to remain cancer free beyond a decade after receiving their first infusion. Clinical trials supporting registration of CAR-T therapies have exclusively examined “total” immunogenicity, results of which did not correlate well with clinical benefits. There is an urgent need from regulators and drug developers to utilize functional (e.g., cell-based) reporter assays to detect potentially neutralizing anti-CAR antibodies to establish the relationship more conclusively between observed immunogenicity and clinical responses for next generation of CAR-T therapies. We described the development and validation of a functionally relevant, sensitive, and reproducible cell-based assay for the qualitative determination of potentially neutralizing antibodies to CAR19. Assay system and results will be described during the presentation.
Learning Objectives:
Participants will learn new techniques to address functional immunogenicity in CAR-T therapies that aim to alleviate past discrepancies between humoral immunogenicity studies and clinical efficacy and safety data.
Participants will understand the need to meet increased scrutiny from regulatory agencies to test for potential neutralizing antibodies in CAR-T therapies and how this testing can impact drug labeling.
Focusing on bioanalytical strategies to overcome challenges in developing and validating complex multi-cell assay systems, participants will gain insight into novel modalities to address immunogenicity in cell and gene therapies.