The E6 and E7
proteins of high-risk human papillomavirus (HPV) types are thought to be the ideal sources of
antigens for
immunotherapy for
cervical cancer since they are expressed by the
tumors and not by normal cells. We recently described new HPV 16
epitopes, including the E6 52-61
peptide restricted by HLA class I molecule B57. Primary tumor cell lines were established from three
HLA-B57 positive, HPV 16 positive
cervical cancer patients, and their recognition by a E6 52-61 specific CD8+ T cell clone was determined using a
chromium release assay and an IFN-gamma
enzyme-linked immunospot (ELISPOT) assay. The recognition of homologous
epitopes contained in other high-risk HPV types (18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 73) was also examined at the
peptide level. A low level of killing of two of the tumor cell lines derived from the three patients was demonstrated using a
chromium release assay. The level of killing of one of these tumor cell lines was enhanced upon treatment with IFN-gamma and/or the addition of
antigen. This tumor cell line also induced measurable IFN-gamma secretion. The recognition of homologous
epitopes from HPV 35, 39, 45, 51, and 73 was detected in an ELISPOT assay. Therefore, the HPV 16 E6 52-61
epitope appears to be at least weakly expressed by tumor cell lines derived from
cervical cancer, and the HPV 16 E6 52-61-specific T cell clone can recognize homologous
peptides derived from other high risk HPV sequences.