ASCPT Members-Only Webinar Presented by the Biologics, Oncology (ONC), Pharmacometrics & Pharmacokinetics (PMK), and Systems Pharmacology (SP) Communities
Speakers: Philipp Altrock, PhD, and Xu (Sue) Zhu, PhD
Moderators: Antari Khot, PhD, and Daniel Kirouac, PhD
Chimeric Antigen Receptor T-cells (CAR-T) have shown remarkable activity in the treatment of B-cell malignancies. With four approved therapies and hundreds in clinical development for other hematological and solid tumors, genetically engineered T-cells are changing the drug development landscape. However, T-cells make highly unwieldly therapeutics. These ‘living drugs’ proliferate, differentiate, actively traffic between tissues and communicate with patient immune systems while executing function. As a result of this complexity, there is little relationship between administered dose and exposure. Exposure and response are driven by a combination of host-factors (lymphodepletion, tumor burden and patient-specific microenvironments) and cell-intrinsic properties of the infused product (differentiation state and composition, CAR design and resultant “tonic” signaling from the engineered receptors). By examining the pharmacology of CAR-Ts we can learn much about the biology of T-cells, and the immune system more broadly.
This session will address challenges toward developing and clinically employing CAR-T therapies, namely: how dynamic interactions between CAR-Ts, tumor and patient lymphocytes drive exposure and response; and strategies for FIH dose prediction given the complexity of these product-host interactions.
Learning Objectives: 1. Understand how the unique pharmacology of CAR-T therapies emanate from the underlying biology of T-cells and their interactions with patient immune systems. 2. Lessons gleaned from the first-generation of CAR-Ts are being employed to improve PKPD translation and FIH dosing strategies.