Inhibition of mouse RM-1 prostate cancer and B16F10 melanoma by the fusion protein of HSP65 & STEAP1 186-193

Biomed Pharmacother. 2019 Mar:111:1124-1131. doi: 10.1016/j.biopha.2019.01.012. Epub 2019 Jan 12.

Abstract

The research of tumor vaccine plays a crucial role in tumor immunotherapy. This study has constructed and prepared a fusion protein vaccine of heat shock protein 65 (HSP65) and the octapeptide epitope 186-193 of the six transmembrane epithelial antigen of the prostate 1 (STEAP1 186-193), and investigated the inhibitory effect of the fusion protein on mouse RM-1 prostate cancer and B16F10 melanoma xenografts. The fusion protein His-HSP65-STEAP1 186-193 (HHST1), His-HSP65-2×STEAP1 186-193 (HHST2) and His-HSP65-6×STEAP1 186-193 (HHST6) were obtained by setting different copy number of STEAP1 186-193 and adding His purification tag before HSP65. Firstly the inhibitory effect of fusion protein on mouse RM-1 prostate cancer xenografts has been studied, which could be the basis of the study the inhibitory effect of the best fusion protein on mouse B16F10 melanoma xenografts. All studies compared with the fusion protein His-HSP65 (HHSP65), the fusion proteins HHST1, HHST2 and HHST6 all could significantly inhibit the growth of mouse RM-1 prostate cancer xenografts. In addition, the fusion protein HHST2 was proved to be the best compared with the fusion proteins HHST1 and HHST6 (P<0.05). Apart from this, compared with the fusion protein HHSP65, the fusion protein HHST2 also significantly inhibited the growth of mouse beared B16F10 melanoma. The results above indicate that HSP65 and STEAP1 186-193 can significantly inhibit the growth of mouse RM-1 prostate cancer and B16F10 melanoma xenografts, and the appropriate increase of copy number can effectively improve that the fusion protein has an excellent anti-tumor ability.

Keywords: Heat shock protein 65 (HSP65); Immunotherapy; Melanoma; Prostate cancer; STEAP1; Vaccine.

MeSH terms

  • Animals
  • Antigens, Neoplasm / pharmacology*
  • Cancer Vaccines / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Heat-Shock Proteins / pharmacology*
  • Immunotherapy / methods
  • Male
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Prostate / drug effects*
  • Prostate / immunology
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / therapy*
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Heat-Shock Proteins
  • Recombinant Fusion Proteins
  • Steap protein, mouse
  • heat shock protein-65, mouse