Dr. Marissa Renardy

Marissa Renardy 

Date: Tuesday March 19, 2024 at 4:00 PM Eastern Time

Join by Zoom: https://ufl.zoom.us/j/96123363118

Speaker: Marissa Renardy, Ph.D., Principal Scientist

Affiliation: Modeling, Applied BioMath

Title: A multi-scale semi-mechanistic CK/PD model for CAR T-cell therapy

Abstract: Chimeric antigen receptor T (CAR T) cell therapy has shown remarkable success in treating various leukemias and lymphomas. Cellular kinetic (CK) and pharmacodynamic (PD) behavior of CAR T cell therapy is distinct from other therapies due to its living nature. CAR T CK is characterized by an exponential expansion driven by target binding, fast initial decline (contraction), and slow long-term decline (persistence). Due to the dependence of CK on target binding, CK and PD of CAR T therapies are inherently and bidirectionally linked. In this work, we develop a semi-mechanistic model of CAR T CK/PD, incorporating molecular-scale binding, T cell dynamics with multiple phenotypes, and tumor growth and killing. We calibrated this model to published CK and efficacy data for a CD19-targeting CAR T cell therapy. Using local and global sensitivity analyses, we explore variability in response due to patient- and drug-specific properties.