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Induction of Antitumor Immunity Against Cervical Cancer by Protein HPV-16 E7 in Fusion With Ricin B Chain in Tumor-Bearing Mice

Sadraeian, Mohammad Msc*; Rasoul-Amini, Sara PhD*†‡; Mansoorkhani, Mohammad Javad Khoshnood PhD§; Mohkam, Milad PhDc*†; Ghoshoon, Mohammad Bagher PhDc*†; Ghasemi, Younes PhD*†

International Journal of Gynecological Cancer: June 2013 - Volume 23 - Issue 5 - p 809–814
doi: 10.1097/IGC.0b013e3182907989
Basic Science

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.

*Pharmaceutical Sciences Research Center, †Department of Pharmaceutical Biotechnology, ‡Department of Medicinal Chemistry, and §Department of Pharmacology Toxicology, School of Pharmacy, Shiraz University of Medical Science, Shiraz, Iran.

Address correspondence and reprint requests to Younes Ghasemi, PhD, Department of Pharmaceutical Biotechnology and Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, PO Box 71345-1583, Shiraz, Iran. E-mail: ghasemiy@sums.ac.ir.

This work was supported by a grant from the Research Council of Shiraz University of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

The authors declare no conflicts of interest.

Received January 16, 2013

Accepted March 5, 2013

Copyright © 2013 by IGCS and ESGO