Predictive and Therapeutic Biomarkers in CAR T-Cell Therapy

This 30-minute presentation is one of the four presentations in a two-hour symposium, which is proposed by Drs. Yow-Ming Wang and Xiaofei Wang. The title of the two-hour symposium is "Biomarkers for Cancer Immunotherapy".

Chimeric antigen receptor (CAR) T cell therapy represents a breakthrough in immunotherapy with the potential of ushering into a new era of cancer treatment. Translational drug- and disease-specific biomarkers not only hold the potential to inform patient selection with CAR-T cell therapy but could also be monitored to evaluate effectiveness of treatments and predict incidences of side effects. Quantitative understanding of these biomarkers can therefore not only contribute towards optimizing therapeutic and prognostic strategies for CAR-T cell therapy but could also be leveraged to identify early signals of clinical activity and adverse events.

Biomarkers can vary from effective indicators of patients’ baseline characteristics, overall tumor burden and tumor kinetics, signal(s) of CAR-T cell activation, proliferation and potency, modulation of immune microenvironment, signal(s) of adverse events etc. Quantitative correlations of drug- and disease associated biomarkers with CAR-T cellular kinetics and response endpoints could enable decision making associated with proof of mechanism (POM) and early signals of clinical activity. Such biomarker analysis could also facilitate recommended phase-2 dose (RP2D) selection and when integrated within Quantitative Systems Pharmacology (QSP) models, they could enable reverse translation.

Within this presentation, presenter will discuss some key clinical case studies in hematological malignancies and solid tumors, where drug- and disease-specific biomarkers play an evident role in determining ‘signals of activity’ associated with CAR-T cell therapies. Application of longitudinal biomarker dataset(s) within multiscale mechanistic CK-PD models will also be discussed.