Synergically enhanced anti-tumor immunity of in vivo panCAR by circRNA vaccine boosting.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy has shown promise in treating hematologic malignancies, but it still faces challenges, including high costs, a time-consuming manufacturing process, and the necessity of lymphodepletion. Here, we generate circular RNAs (circRNAs) encoding CAR proteins, referred to as circRNA^CAR, which mediates remarkable tumor killing in human primary T cells. We demonstrate that circRNA^CAR, delivered with immunocyte-tropic lipid nanoparticles (LNPs), can form in vivo panCAR cells (CAR-T, CAR-natural killer [NK], and CAR-macrophage), significantly inhibit tumor growth, and reshape the tumor microenvironment in mice. Importantly, combining in vivo panCAR with circRNA-based vaccines encoding the corresponding HER2 antigens exhibits synergis

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12432353 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature