Preparation of a new combination nanoemulsion-encapsulated MAGE1-MAGE3-MAGEn/HSP70 vaccine and study of its immunotherapeutic effect

Pathol Res Pract. 2020 Jun;216(6):152954. doi: 10.1016/j.prp.2020.152954. Epub 2020 Apr 17.

Abstract

Background: MAGE family genes have been studied as targets for tumor immunotherapy for a long time. Here, we combined MAGE1-, MAGE3- and MAGEn-derived peptides as a cancer vaccine and tested whether a new combination nanoemulsion-encapsulated vaccine could be used to inhibit the growth of tumor cells in humanized SCID mice.

Methods: The nanoemulsion-encapsulated complex protein vaccine (MAGE1, MAGE3, and MAGEn/HSP70 fusion protein; M1M3MnH) was prepared using a magnetic ultrasonic technique. After screening, human PBMCs were injected into SCID mice to mimic the human immune system. Then, the humanized SCID mice were challenged with M3-HHCC cells and immunized with nanoemulsion-encapsulated MAGE1-MAGE3-MAGEn/HSP70 [NE(M1M3MnH)] or M1M3MnH. The cellular immune responses were detected by IFN-γ ELISPOT and cytotoxicity assays. Therapeutic and tumor challenge experiments were also performed.

Results: The results showed that the immune responses elicited by NE(M1M3MnH) were apparently stronger than those elicited by M1M3MnH, NE(-) or PBS, suggesting that this novel nanoemulsion carrier induces potent antitumor immunity against the encapsulated antigens. The results of the therapeutic and tumor challenge experiments also indicated that the new vaccine had a definite effect on SCID mice bearing human hepatic cancer.

Conclusion: Our study indicated that the combination of several tumor antigen-derived peptides may be a relatively good strategy for peptide-based cancer immunotherapy. These results suggest that the complex nanoemulsion vaccine could have broader applications for both therapy and prevention mediated by antitumor effects in the future.

Keywords: MAGE; Nanoemulsion; Tumor; Vaccine.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / pharmacology*
  • Cancer Vaccines / pharmacology*
  • Emulsions
  • Female
  • HSP70 Heat-Shock Proteins / immunology
  • HSP70 Heat-Shock Proteins / pharmacology*
  • Humans
  • Melanoma-Specific Antigens / immunology
  • Melanoma-Specific Antigens / pharmacology*
  • Mice
  • Mice, SCID
  • Nanoparticles
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / pharmacology*
  • Neoplasms, Experimental
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Emulsions
  • HSP70 Heat-Shock Proteins
  • MAGEA1 protein, human
  • MAGEA3 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins