A synthetic chimeric peptide harboring human papillomavirus 16 cytotoxic T lymphocyte epitopes shows therapeutic potential in a murine model of cervical cancer

Abstract

Infection with human papillomavirus (HPV) such as HPV16 is known to be associated with cervical cancer. The E6 and E7 oncoproteins of this virus are attractive targets for T-cell-based immunotherapy to cervical cancer. In our study, software predicted, multiple H-2D(b) restricted HPV16 cytotoxic T lymphocytes (CTL) epitopes on a synthetic chimeric peptide, was used along with different immunopotentiating adjuvants such as alum, heat-killed Mycobacterium w (Mw) cells, and poly D,L-lactic-co-glycolide (PLGA) microspheres. We have shown that subcutaneous immunization with H-2D(b)-restricted HPV16 peptide was able to generate CTL-mediated cytolysis of HPV16 E6- and E7-expressing TC-1 tumor cells in vitro, as well as protect against in vivo challenge with TC-1 cells in C57BL/6 mice. In vitro, this chimeric peptide showed best efficacy with PLGA microspheres, moderate with alum, and least with Mw as adjuvant. This approach may thus provide a potential peptide-based therapeutic candidate vaccine for the control of HPV infection and hence cervical cancer.