An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors
Menée à l'aide de modèles murins, cette étude met en évidence l'intérêt d'un vaccin à ARN pour favoriser l'expansion des lymphocytes CAR-T ciblant la protéine de jonction étroite "claudine 6" et améliorer leur efficacité contre les tumeurs solides
Chimeric antigen receptor (CAR)-T cells have shown efficacy in patients with B cell malignancies. Yet their application for solid tumors has challenges that include limited cancer-specific targets and non-persistence of adoptively transferred CAR-T cells. Here we introduce the developmentally regulated tight junction protein claudin 6 (CLDN6) as a CAR target in solid tumors, and a strategy to overcome inefficient CAR-T cell stimulation in vivo. We demonstrate that a nanoparticulate RNA vaccine, designed for body-wide delivery of the CAR antigen into lymphoid compartments, stimulates adoptively transferred CAR-T cells. Presentation of the natively folded target on resident dendritic cells promotes cognate and selective expansion of CAR-T cells. Improved engraftment of CAR-T cells and regression of large tumors in difficult-to-treat mouse models was achieved at sub-therapeutic CAR-T cell doses.