Induction of the immune response against HPV16-associated tumours with experimental vaccines

5 Induction of the immune response against HPV16-associated tumours with experimental vaccines The E6/E7 oncoproteins of human papillomaviruses are expressed in most trans- formed cells of cervical carcinoma and, therefore, are attractive targets for T cell-mediated immunotherapy. We have investigated the capacity of vaccines based on E7 oncoprotein- derived peptides to induce cellular immune responses and their therapeutic potential for treatment of minimal residual disease after surgery in a murine experimental model mi- micking human HPV16-associated carcinomas. We compared the effect of E749-57 peptide (RAHYNIVTF) exhibiting immunodominant epitope recognized by cytotoxic T lymphocy- tes with E744-62 peptide (QAEPDRAHYNIVTFCCKCD = 8Q) exhibiting CTL, TH and B- cell epitopes. Immune responses were compared in healthy mice and in mice after surgery or chemotherapy of tumours with ifosfamide derivative CBM-4A. Cellular immune re- sponses were monitored in spleen cells of C57BL/6 mice using ELISPOT-IFN-γ and 51 Cr- release assay. Flow cytometry was used for the detection of CD4+ , CD8+ , CD4+ CD25+ , Gr-1+ CD11b+ and CD3+ NK1.1+ populations. Vaccination with 8Q peptide and synthetic CpG oligodeoxynucleotide as adjuvant induced stronger antitumour immune responses than immunodominant CTL epitope alone in both..