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Cancer
Immunity, Vol. 6, p. 9 (30 June 2006) Submitted:
2 September 2005. Resubmitted: 28 April 2006. Accepted:
2 June 2006.
Communicated by: CJM Melief
Recognition of a cervical cancer derived tumor cell line by a human papillomavirus type 16 E6 52-61-specific CD8 T cell clone
Kevin H. Kim1, Ryan Dishongh2,
Alessandro D. Santin3, Martin J. Cannon2,3,
Stefania Bellone3, and Mayumi Nakagawa1,4
1Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
2Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
3Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
4Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Keywords:
human, cervical cancer, cultured tumor cells, HPV type 16, cytotoxic T lymphocytes, epitope analysis
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Abstract
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-γ 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-γ and/or the addition of antigen. This tumor cell line also induced measurable IFN-γ 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.
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