Rapid‐Turnaround Co‐Administration of mRNA‐Based MHC‐I and MHC‐II‐Restricted Neoantigens Enhances Immune Responses of Antigen‐Specific CD8 + T Cells and Anti‐Cancer Efficacy in Colorectal Cancer

Abstract

Abstract Personalized cancer vaccines (PCVs) represent a promising frontier in cancer immunotherapy; however, challenges in neoantigen prediction and treatment optimization persist. This study aims to introduce an innovative mRNA‐based PCV platform that addresses these limitations. Co‐administration of our major histocompatibility complex (MHC)‐I and MHC‐II‐restricted neoantigens increases antigen‐specific T cell responses and exhibits strong anti‐cancer efficacy, significantly inducing antigen‐specific CD8 + T cell‐immune responses. The mRNA‐based vaccine targeting the novel antigens demonstrates anti‐tumor efficacy in a murine model of colorectal cancer and reduces post‐surgery recurrence in mRNA‐vaccinated mice. Notably, early‐stage vaccination induces a striking anti‐cancer effect, underscoring the critical role of MHC‐II neoantigens alongside MHC‐I antigen prediction in shaping effective anti‐tumor immunity, in the activation of antigen‐specific CD8 + T cells. In addition, the combination of immune checkpoint inhibitors and the vaccine synergistically inhibits tumor growth by inducing robust T cell responses and promoting favorable alterations in the tumor microenvironment. Taken together, the results provide a strong rationale for the clinical investigation of rapid‐turnaround co‐administration of MHC‐I/II‐restricted neoantigens‐based mRNA vaccines in colorectal cancer, as supported by the anti‐tumor efficacy of early‐stage application and combination immunotherapy approaches.

Abstract of "Rapid‐Turnaround Co‐Administration of mRNA‐Based MHC‐I and MHC‐II‐Restricted Neoantigens Enhances Immune Responses of Antigen‐Specific CD8 + T Cells and Anti‐Cancer Efficacy in Colorectal Cancer" by Seongje Cho, Woori Kwak, Hyunho Yoon et al., https://doi.org/10.1002/advs.202506426, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.