Genetically Engineered Cytomembrane Nanovaccines for Cancer Immunotherapy.

Cancer nanovaccines have attracted widespread attention by inducing potent cytotoxic T cell responses to improve immune checkpoint blockade (ICB) therapy, while the lack of co-stimulatory molecules limits their clinical applications. Here, we report a genetically engineered cancer cytomembrane nanovaccine that simultaneously overexpresses co-stimulatory molecule CD40L and immune checkpoint inhibitor PD1 to elicit robust antitumor immunity for cancer immunotherapy. The CD40L and tumor antigens inherited from cancer cytomembranes effectively stimulated dendritic cell (DC)-mediated immune activation of cytotoxic T cells, while the PD1 on cancer cytomembranes significantly blocked PD1/PD-L1 signaling pathway, synergistically stimulating antitumor immune responses. Benefited from the targeting ability of cancer cytomembranes, this nanovaccines formula showed an enhanced lymph nodes trafficking and retention. Compared with original cancer cytomembranes, this genetically engineered nanovaccine induced 2-fold DC maturation and showed satisfactory precaution efficacy in a breast tumor mouse model. This genetically engineered cytomembrane nanovaccine offers a simple, safe, and robust strategy by incorporation of cytomembrane components and co-stimulatory molecules for enhanced cancer immunotherapy. This article is protected by copyright. All rights reserved.