Dying tumor cells-inspired vaccine for boosting humoral and cellular immunity against cancer

J Control Release. 2023 Jul:359:359-372. doi: 10.1016/j.jconrel.2023.05.044. Epub 2023 Jun 14.

Abstract

Whole tumor cells can act as effective antigen depots and have been regarded as prospective candidate for cancer vaccines. However, the clinical outcomes of whole tumor cell vaccine were restricted by the poor immunogenicity and potential in vivo oncogenicity risks. Herein, a simple and effective cancer vaccine named frozen dying tumor cells (FDT) was constructed to initiate a cascade of immune attacks against cancer. By introducing immunogenic dying tumor cells and integrating cryogenic freezing technology, FDT was endowed with high immunogenicity, good in vivo safety, and long-time storage superiority. In syngeneic mice with malignant melanoma, FDT primed the polarization of follicular helper T cells and the differentiation of germinal center B cells in lymph nodes, and promoted the infiltration of cytotoxic CD8+ T cells in the tumor microenvironment, triggering the dual activation of humoral and cellular immunity. Of note, when combined with cytokines and immune checkpoint inhibitors, the FDT vaccine achieved 100% eradication of pre-existing tumors in mice, as demonstrated in the peritoneal metastasis model of colorectal carcinoma. Taken together, our work suggests an efficient cancer vaccine inspired by dying tumor cells and provides an alternative treatment candidate for cancer.

Keywords: Cancer vaccine; Cryogenic freezing technique; Doxorubicin; Dying tumor cells; Immunogenic cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Cancer Vaccines* / therapeutic use
  • Immunity, Cellular
  • Immunity, Humoral
  • Melanoma* / drug therapy
  • Mice
  • Tumor Microenvironment

Substances

  • Cancer Vaccines