Physiologically based pharmacokinetic model for CAR-T cell delivery and efficacy in solid tumors.

ABSTRACT: Abnormal blood vessels limit the delivery and function of endogenous T cells as well as adoptively transferred Chimeric Antigen Receptor (CAR)-T cells in tumor microenvironment (TME). We recently showed that vascular normalization using anti-VEGF therapy can overcome these challenges and improve the outcome of CAR-T therapy in glioblastoma models in mice. Here, we developed a physiologically based pharmacokinetic model to simulate the dynamics of both adoptively transferred CAR-T cells and endogenous immune cells in solid tumors following vascular normalization. Similar to our data, our model simulations show that vascular normalization reprograms the TME from immunosuppressive to immunosupportive by enhancing infiltration of endogenous CD8⁺ T cells and CAR-T cells, increasing M

SUBMITTER: Hadjigeorgiou AG 

PROVIDER: S-EPMC12646303 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature