Anchoring a Xenogeneic Antigen‐Guided Immune Activation System to Tumor Cell Membrane for Solid Tumor Treatment

Abstract The low immunogenicity of tumor antigens and their limited expression on the surface of tumor cells are important reasons for the low response rate of cancer immunotherapy, especially for solid tumors. Here, a physical anchoring strategy to label a safe xenogeneic antigen to the surface of tumor cells in vivo for effective and selective guide of immune response is demonstrated. Specifically, dandelion‐like nanovesicle (DNV‐OVA) assembled by amphiphilic Au‐Fe 3 O 4 Janus nanoparticles as the anchoring device and employing ovalbumin (OVA) as a model antigen is constructed. The DNV‐OVA plays two important roles in body. It labels “non‐self” signals (OVA, 51.0%) to tumor cell surface, thereby effectively inducing antibody dependent cell‐mediated cytotoxicity (ADCC). In parallel, the ADCC mechanism releases tumor antigens from lysed tumor cells, which are phagocytosed by dendritic cells and selectively activate T cells. These T cells precisely control the proliferation of residual tumor cells. Anchoring xenogeneic antigens to tumor cells is a universal approach applicable to a broad range of solid tumors.