Development of minimal physiologically-based pharmacokinetic-pharmacodynamic models for characterizing cellular kinetics of CAR T cells following local deliveries in mice.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of hematologic malignancies and have potentials for solid tumor treatment. To overcome limited CAR T cell infiltration to solid tumors, local delivery of CAR T cells is a practical strategy that has shown promising therapeutic outcome and safety profile in the clinic. It is of great interest to understand the impact of dosing routes on CAR T cell distribution, subsequent proliferation and tumor killing in a quantitative manner to identify key factors that contribute to CAR T efficacy and safety. In this study, we established mouse minimal physiologically-based pharmacokinetic (mPBPK) models combined with pharmacodynamic (PD) components to delineate CAR T cell distribution, proliferation, tumor growth, and tu

SUBMITTER: Tsai CH 

PROVIDER: S-EPMC9508025 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature