DNA Nanostructures‐Based In Situ Cancer Vaccines: Mechanisms and Applications

Abstract Current tumor vaccines suffer from inadequate immune responsive due to the insufficient release of tumor antigens, low tumor infiltration, and immunosuppressive microenvironment. DNA nanostructures with their ability to precisely engineer, controlled release, biocompatibility, and the capability to augment the immunogenicity of tumor microenvironment, have gained significant attention for their potential to revolutionize vaccine designing. This review summarizes various applications of DNA nanostructures in the construction of in situ cancer vaccines, which can generate tumor‐associated antigens directly from damaged tumors for cancer immune‐stimulation. The mechanisms and components of cancer vaccines are listed, the specific strategies for constructing in situ vaccines using DNA nanostructures are explored and their underlying mechanisms of action are elucidated. The immunogenic cell death (ICD) induced by chemotherapeutic agents, photothermal therapy (PTT), photodynamic therapy (PDT), and radiation therapy (RT) and the related cancer vaccines building strategies are systematically summarized. The applications of different DNA nanostructures in various cancer immunotherapy are elaborated, which exerts precise, long‐lasting, and robust immune responses. The current challenges and future prospectives are proposed. This review provides a holistic understanding of the evolving role of DNA nanostructures for in situ vaccine development.