Induction of antitumor immunity against cervical cancer by protein HPV-16 E7 in fusion with ricin B chain in tumor-bearing mice

Int J Gynecol Cancer. 2013 Jun;23(5):809-14. doi: 10.1097/IGC.0b013e3182907989.

Abstract

Objective: In immunotherapy of HPV-16-associated cervical cancers, the E7 protein is considered as a prime candidate. However, it is a poor inducer of a cytotoxic T-cell response when used as a singular antigen in protein vaccination. Therefore, to design effective cancer vaccines, the best tumor antigens should be combined with the most effective immunogens or drug delivery tools to achieve positive clinical results. In this study, we fused HPV-16 E7 with the lectin subunit of ricin toxin (RTB) from castor plant as a vaccine adjuvant/carrier.

Materials and methods: After reaching the soluble form of the recombinant protein, we designed 2 preventive and inhibition tumor models for investigation of the prevention and rejection of TC-1 cell growth in female C57BL/6 mice, respectively. In each model, mice were immunized with the recombinant protein of E7-RTB or E7 without any adjuvant.

Results: We demonstrated that prophylactic immunization of E7-RTB protected mice against challenge from TC-1 cells. Also in the therapeutic model, E7-RTB could inhibit TC-1 tumor growth in the lung. The results were significant compared with the immunization of E7 singularly.

Conclusions: We concluded that immunization with E7-RTB protein without any adjuvant could generate antitumor effects in mice challenged with TC-1 cells. This research verifies the clinical applications and the future prospects for development of HPV-16 E7 therapeutic vaccines fused to immunoadjuvants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunization
  • Immunotherapy*
  • Mice
  • Mice, Inbred C57BL
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / immunology*
  • Papillomavirus E7 Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Recombinant Fusion Proteins / metabolism
  • Ricin / genetics
  • Ricin / immunology*
  • Ricin / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / prevention & control*

Substances

  • Cancer Vaccines
  • Papillomavirus E7 Proteins
  • Recombinant Fusion Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • Ricin