Physiologically-based pharmacokinetic model for CAR-T cells 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 the 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-enhancing infiltration of endogenous CD8⁺ T cells and CAR-T cells, increasing

SUBMITTER: Hadjigeorgiou AG 

PROVIDER: S-EPMC12393523 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature