Targeting fibroblast activation protein in solid tumors via LNP-mediated CAR-mRNA delivery promotes durable regression in murine models.

ABSTRACT: The therapeutic potential of chimeric antigen receptor (CAR) T-cell therapy in treating solid tumors is highly recognized, yet the complex and immunosuppressive nature of the tumor microenvironment, poor accessibility, and the instability of target antigens pose substantial challenges. Here, we present an mRNA-LNP-based therapeutic strategy that delivers mRNA encoding a fibroblast activation protein (FAP)-specific CAR to reprogram host immune cells in vivo and target cancer-associated fibroblasts within the tumor stroma. In multiple solid tumor mouse models, this approach, combined with chemotherapeutic agents and immune checkpoint inhibitors, achieved significant tumor regression and induced durable, antigen-specific immune memory. Incorporation of m⁶A-modified CAR mRNA acceler

SUBMITTER: Meng S 

PROVIDER: S-EPMC12800119 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature