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

Acta Biomater. 2022 Jan 15:138:491-504. doi: 10.1016/j.actbio.2021.10.041. Epub 2021 Oct 30.

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.

Keywords: Dendritic cells-derived exosomes; MUC1 antigen; Vaccine adjuvant; Vaccine carrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Cancer Vaccines*
  • Dendritic Cells
  • Exosomes*
  • Immunity, Cellular
  • Immunity, Humoral
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms* / therapy
  • Vaccines, Conjugate

Substances

  • Cancer Vaccines
  • Vaccines, Conjugate