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.

Engineered outer membrane vesicle is potent to elicit HPV16E7-specific cellular immunity in a mouse model of TC-1 graft tumor

“…Based on the delivery platform, immune responses can be modulated by modifying the stability, tissue and cell targeting, and the dendritic cell (DC) activation of antigen and adjuvant, and they can improve the microenvironment to facilitate the development of antitumor immunity. Largely, E7 peptides, instead of whole E7 proteins, have been carried by a variety of nanoparticles such as recombinant virus-like particles [7][8][9][10][11] or artificial particles, 12 which are limited by the compatibility of the particles. A good prospect would be a long peptide or even the full-length E7 protein, which holds more epitopes, and other novel nanoparticle platforms thus need to be explored.…”

A truncated fragment of Ov-ASP-1 consisting of the core pathogenesis-related-1 (PR-1) domain maintains adjuvanticity as the full-length protein

“…Vaccination has been the most effective and economical strategy to prevent or treat a variety of infections [1]. In recent years, the development of protein-or peptide-based subunit vaccines has become of great interest due to their improved safety; however, they typically elicit a weak or modest antibody response with little, or no, T cell response on their own [2][3][4]. Thus, adjuvants have to be added to their formulations to improve the efficacy of these new generation subunit vaccines [1].…”

Hepatitis C virus E2 protein encapsulation into poly D, L-lactic-<em>co</em>-glycolide&nbsp;microspheres could induce mice cytotoxic T-cell response

“…Moreover, for a therapeutic vaccine, PLGA microspheres have successfully demonstrated adjuvant activity to enhance immune responses to human papillomavirus type 16 (HPV16) protein in mice. 19 PLGA particles have been shown to effectively process the antigens in vitro to murine bone marrow-derived APCs because of their slow degradation rate before the internalization in APCs. 30,31 This suggests that PLGA particles are effective and useful for immunotherapy.…”

“…This result is related to the previous report that PLGA microspheres can induce higher IFN-γ in murine models. 19 IFN-γ, one of the key regulatory cytokines in the host immune response against viral infections, is secreted by effector CD8…”

“…17,18 For the viral therapeutic vaccine, an interesting study in HPV16-E6 and -E7 peptides combined with PLGA microspheres has shown a higher efficacy when compared with peptides alone in murine models. 19 Therefore, PLGA particles could have a great potential as protein carriers and adjuvant for an HCV subtype 1b therapeutic vaccine. In this study, we generate an HCV genotype 1b protein because this genotype plays an important role in HCC development, especially in patients with early-stage liver disease.…”