An efficient and safe MUC1-dendritic cell-derived exosome conjugate vaccine elicits potent cellular and humoral immunity and tumor inhibition in vivo

Abstract Antitumor vaccines are a promising strategy for preventing or treating cancers by eliciting antitumor immune responses and inducing protective immunity against specific antigens expressed on tumor cells. Vaccine formulations that enhance the humoral and cellular immune responses of vaccine candidates would be highly beneficial but are still limited. Here we developed an antitumor vaccine candidate by conjugating a MUC1 glycopeptide antigen to dendritic cell-derived exosomes (Dex). In vivo, the MUC1-Dex construct induced high MUC1-specific IgG antibody titers with strong binding affinities for MUC1-positive tumor cells and promoted cytokine secretion. Moreover, CD8+ T cells from immunized mice exhibited strong cytotoxicity against MUC1-positive tumor cells. Importantly, in both preventative and therapeutic tumor-bearing mouse models, the construct inhibited tumor growth and prolonged survival. Collectively, these results demonstrate that Dex is a promising vaccine carrier that can be used as adjuvant to enhance the immunological efficacy of tumor vaccines. Statement of significance • We prepared an efficient and biosafe antitumor vaccine candidate by conjugating Dex with MUC1 glycopeptide using a two-step biorthogonal crosslinking strategy. • MUC1-Dex enhanced the expression of costimulatory molecules CD80 and CD86 on DCs to promote their maturation whilst simultaneously upregulating MHC I and MHC II expression to increase antigen presentation by DCs. • MUC1-Dex conjugates stimulated the production of MUC1-specific IgG antibodies in vivo, and the antibodies bound strongly to MUC1-expressing tumor cells. • The constructed vaccines induced a strong antibody response and antigen specific CTLs to kill the tumor and delayed tumor development in a therapeutic and prophylactic tumor bearing mouse model.