Challenges and Opportunities with Preclinical to Clinical Translation of CAR-T Cell Therapy

Chimeric antigen receptor (CAR) T cell therapy represents a breakthrough in immunotherapy with the potential of ushering into a new era of cancer treatment. So far 6 CAR-T cell therapy products are approved by US FDA and >1000 CAR constructs are in clinical development. These modalities present a unique dose-exposure-response relationship and preclinical animal models may not be reflective of the complex biology of autologous cell therapy products in clinic. Moreover, the process for CAR-T cell manufacturing may be significantly different preclinical and clinical setting rendering different product functionalities. Hence traditional allometric scaling principles may not apply for cell therapies.
Within the first part of presentation, presenter will discuss current practices on determining safe starting dose of CAR-T cell therapy in the clinic, which are empirical in nature and based on prior clinical experience with competitor’s product using literature. The 2nd part of the presentation will be application of mechanism-based PK-PD modeling to characterize preclinical-to-clinical translational bridge for one unique CAR Clone having both preclinical and clinical functional data