CCR2/CXCR6 enhances tumor infiltration and antitumor efficacy of MSLN CAR-T cells.

ABSTRACT: Chimeric antigen receptor T (CAR-T) cell therapy has shown promise in treating solid tumors, but the clinical success is often limited by insufficient tumor infiltration. In this study, we sought to engineered two MSLN-targeted CAR-T cell variants, Intra2 and Intra6, expressing CCR2 and CXCR6, respectively, to improve their migration toward the tumor microenvironment. Flow cytometry confirmed stable receptor expression. In vitro assays demonstrated that both Intra2 and Intra6 CAR-T cells exhibited significantly improved functional phenotype, migration and invasion, as well as persistence in killing target cells compared to conventional MSLN CAR-T cells. Notably, in vivo, Intra6 CAR-T cells displayed superior antitumor effects, showing enhanced tumor suppression and reduced exhaustion. RNA

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12748374 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature