Synthetic peptides induce a cytotoxic response against human papillomavirus type-18.

Objectives: Over 90% of cervical carcinomas express human papillomavirus (HPV) E6 and E7 proteins. These unique antigens are ideal targets for the development of cytotoxic T-lymphocytes (CTL) for antitumor immunotherapy. In this study we identify peptides from HPV-18 E6 and E7 proteins that bind to HLA class I molecules. We further show that these peptides are able to induce peptide-specific CTL from an HLA-A2-positive (+) peripheral blood donor in vitro.

Methods: A computer-assisted algorithm was devised to identify peptides from HPV-18 E6 and E7 proteins that bind to HLA-A2 molecules. Peptides that were predicted to bind were synthesized and their binding activity was determined. HLA-A2(+) irradiated stimulator cells pulsed with HPV-18 peptides were incubated with HLA-A2(+) peripheral blood mononuclear cells. Cytotoxicity assays were performed to assess specific cell lysis.

Results: Of 295 possible sequences, the computer-assisted algorithm predicted 10 peptides that would have a high probability of binding to HLA-A2. The 4 strongest binding peptides were analyzed for their ability to induce cytotoxic cells against HPV-18 peptide-pulsed targets. Two of the peptides induced significant lysis.

Conclusions: There are limited data on peptide-based immunotherapy for HPV-18(+) tumors. The combination of our computer-assisted algorithm and binding assay permits rapid selection of potential CTL epitopes. We identified two peptides that were able to induce peptide-specific lysis. These two epitopes are candidates for a peptide-based vaccine against HPV-18(+) tumors. The model described has broad applications and can be used in the development of immunotherapy for other types of cancers.