Combining Radiation‐Treated Tumor Vaccines With Mn‐MOF Nanoadjuvants to Amplify Radiation Induced Anti‐Tumor Immune Responses

ABSTRACT Radiotherapy‐induced mutations are critical for neoantigen generation and the initiation of in situ vaccine mediated immune responses; however, their efficacy is severely limited by the immunosuppressive tumor microenvironment. Here, genomic analysis demonstrated that B16F10 tumor cells subjected to in vitro irradiation faithfully recapitulate part of the radiotherapy‐induced mutational landscape observed in subcutaneous tumor models. Based on these findings, a biomimetic cancer vaccine was developed through the integration of RT‐treated tumor cell membranes and manganese‐based metal organic framework nanoadjuvants (Mn@RM). Mn@RM can deliver RT‐induced membrane proteins directly to lymph nodes in order to potentiate the in situ vaccine immune response. Moreover, Mn‐MOF nanoadjuvants enhanced antigen presentation efficiency by nearly two‐fold through activation of the cGAS‐STING pathway in dendritic cells, while Mn@RM further optimized the lymph node immune microenvironment to promote robust anti‐tumor immunity. When combined with radiotherapy and PD‐1 immune checkpoint blockade, Mn@RM demonstrates excellent synergistic tumor treatment effect. Overall, this study offers a promising and clinically translatable platform to augment radiotherapy induced anti‐tumor immunity, particularly for patients receiving radiotherapy in conjunction with surgical interventions.