Tumor Cell Nanovaccines based on Genetically Engineered Antibody-anchored Membrane.

Despite the promise in whole-tumor cell vaccines, a key challenge is to overcome the lack of co-stimulatory signals. Here, we reported agonistic antibody-boosted tumor cell nanovaccines by genetically engineered antibody-anchored membrane (AAM) technology, capable of effectively activating co-stimulatory pathways. Specifically, the AAM can be stably constructed following genetically engineering of tumor cell membranes with anti-CD40 single chain variable fragment (scFv), an agonistic antibody to induce co-stimulatory signals. The nanovaccines were versatilely designed and obtained based on the anti-CD40 scFv-anchored membrane and nanotechnology. Following vaccination, the anti-CD40 scFv-anchored membrane nanovaccines (Nano-AAM/CD40) significantly facilitated the dendritic cell (DC) maturation in CD40-humanized transgenic mice and subsequent adaptive immune responses. Compared to membrane-based nanovaccines alone, the enhanced anti-tumor efficacy in both "hot" and "cold" tumor models of the Nano-AAM/CD40 demonstrated 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 resulted 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 co-stimulatory immune checkpoints. This article is protected by copyright. All rights reserved.