Tumor Cell Nanovaccines Based on Genetically Engineered Antibody‐Anchored Membrane

Abstract Despite the promise in whole‐tumor cell vaccines, a key challenge is to overcome the lack of costimulatory signals. Here, agonistic‐antibody‐boosted tumor cell nanovaccines are reported by genetically engineered antibody‐anchored membrane (AAM) technology, capable of effectively activating costimulatory pathways. Specifically, the AAM can be stably constructed following genetic engineering of tumor cell membranes with anti‐CD40 single chain variable fragment (scFv), an agonistic antibody to induce costimulatory signals. The nanovaccines are versatilely designed and obtained based on the anti‐CD40 scFv‐anchored membrane and nanotechnology. Following vaccination, the anti‐CD40 scFv‐anchored membrane nanovaccine (Nano‐AAM/CD40) significantly facilitates dendritic cell maturation in CD40‐humanized transgenic mice and subsequent adaptive immune responses. Compared to membrane‐based nanovaccines alone, the enhanced antitumor efficacy in both “hot” and “cold” tumor models of the Nano‐AAM/CD40 demonstrates the importance of agonistic antibodies in development of tumor‐cell‐based vaccines. To expand the design of nanovaccines, further incorporation of cell lysates into the Nano‐AAM/CD40 to conceptually construct tumor cell‐like nanovaccines results in boosted immune responses and improved antitumor efficacy against malignant tumors inoculated into CD40‐humanized transgenic mice. Overall, this genetically engineered AAM technology provides a versatile design of nanovaccines by incorporation of tumor‐cell‐based components and agonistic antibodies of costimulatory immune checkpoints.