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

Objectives. Over 90% of cervical carcinomas express human papillomavirus (H PV) E6 and E7 proteins. These unique antigens are ideal targets for the dev elopment of cytotoxic T-lymphocytes (CTL) for antitumor immunotherapy. In t his 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 indu ce peptide-specific CTL from an HLA-A2-positive (+) peripheral blood donor in vitro, Methods. A computer-assisted algorithm was devised to identify peptides fro m HPV-18 E6 and E7 proteins that bind to HLA-A2 molecules. Peptides that we re predicted to bind were synthesized and their binding activity was determ ined. HLA-A2(+) irradiated stimulator cells pulsed with HPV-18 peptides wer e 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 predict ed 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 cyt otoxic cells against HPV-18 peptide-pulsed targets. Two of the peptides ind uced significant lysis. Conclusions, There are limited data on peptide-based immunotherapy for HPV- 18(+) tumors. The combination of our computer-assisted algorithm and bindin g assay permits rapid selection of potential CTL epitopes, We identified tw o peptides that were able to induce peptide-specific lysis. These two epito pes are candidates for a peptide-based vaccine against HPV-18(+) tumors. Th e model described has broad applications and can be used in the development of immunotherapy for other types of cancers. (C) 2001 Academic Press.