Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cylotoxic T Lymphocytes

摘要

The purpose of the research was to identify new ovarian cancer tumor antigens that could be used in the development of an ovarian cancer vaccine. The scope of the work involved identifying peptide antigens recognized by ovarian cancer reactive cytotoxic T lymphocytes (CTL). Eleven ovarian cancer cell lines were characterized for their expression of tumor antigens and MHC molecules This was significant because it provided a resource that could be used for new antigen identification work. CTL were generated against autologous ovarian cancer cells but no evidence was found for the recognition of shared antigens which is significant because this is the type of antigen needed for vaccine development. New methodology was devised for the efficient assessment of the immunogenicity of peptides derived from known protein antigens. This work was significant because it resulted in the identification of two new HLA- A2-restricted antigens derived from TAG-1. It was demonstrated that the treatment of ovarian cancer cells with a demethylating agent is capable of turning on the expression of a large number of cancer/testis antigens and increasing the expression of class I MHC molecules which is significant because known antigens can now be used to target cells that would otherwise escape recognition by CTL.