Membrane-fused and mannose-targeted vesicles as immunoenhanced biomimetic nanovaccines for prevention and therapeutics of melanoma

Abstract

Melanoma is a tumor sensitive to immune response and its immunotherapy has been a research hotspot in recent years. By fusion of melanoma cell membranes and bacterial exosomes through sequential extrusion, we herein design a three-in-one multi-antigenic nanovaccine, namely TBM, to rapidly target immune system. TBM can induce RAW264.7 macrophage cells to differentiate into M1 type cells to release cytotoxic cytokines. It can also promote the maturation and antigen presentation of bone marrow-derived dendritic cells, thus activating spleen T cells to kill B16F10 melanoma cells in vitro. TBM can significantly inhibit the growth and metastasis of melanoma in vivo, and prolong the lifetime of mice, suggesting the preventive effects of vaccines. Further, we integrate cell membranes from mouse melanoma tissues into a novel personalized therapeutic vaccine, namely autologous TBM (ATBM). ATBM combined with Anti PD1 can activate anti-tumor immune response and increase the survival rate of melanoma allografted mice, as supported by eukaryotic reference mRNA-Seq transcriptome sequencing. Generally, this study demonstrates the preventive and therapeutic effects of biomimetic nanovaccines against melanoma, which may be extended to design personalized tumor vaccines for all tumors with immunogenicity, showing great clinical perspectives.