Nanovaccine Showing Potent Immunotherapy to Tumor by Activating ΓδT Cells

Most vaccines are designed to attack tumor cells by activating CD4+/CD8+ alpha beta T cells. Unfortunately, alpha beta T cells, which only recognize the peptide antigens in the complexes with polymorphic MHCI/II molecules, surrender to the tumor heterogenicity. As another subset of T cells, gamma delta T cells become salient in antitumor because of their unique immunotherapeutic roles. Herein, a tumor vaccine is developed with multivalent antigens by fusion of tumor cell membranes with lipids and successfully activated gamma delta T cells via microneedle inoculation. It is certified that the evoked gamma delta T cells synchronize with alpha beta T cells revitalizing tumor-induced immunotolerance. In turn, the tumors of mice are significantly inhibited and their median survival time is prolonged considerably. Moreover, the nanovaccine inhibits tumor recurrence after resection. The therapeutic effects are corroborated with the results from TCR delta(-/-) mice as well as cytokine expression in tumor.