Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cytotoxic T Lymphocytes; Annual rept. 1 Nov 2006-31 Oct 2007

摘要

The purpose of the research is to identify new ovarian cancer tumor antigens that can be used in the immunotherapeutic treatment of ovarian cancer. The scope of this work involves (1) identifying the peptide antigens recognized by ovarian reactive cytotoxic T lymphocytes (CTL); and (2) identify peptide antigens within the Her-2/neu, folate binding protein (FBP), and TAG proteins that give rise to ovarian reactive CTL. Eleven ovarian cancer cell lines were characterized for the expression of class I and II MHC expression, 15 tumor antigens, and immunosuppressive cytokines. This is significant because it will facilitate these and other studies. CTL lines were established from seven patients, but none of them appear to recognize a shared antigen and none recognize any of the predicted antigens from FBP, Her-2/neu, or mesothelin. This is significant because it indicates that ovarian cancer cells may not express shared antigens that can be targeted in a vaccine. The FBP gene was cloned and the DNA demethylating agent 5-aza-2 -deoxycytidine was shown to upregulate cancer testis antigen expression and class I MHC expression on ovarian cancer cells. These results are significant because the ability to upregulate antigens on ovarian cancer cells may make them more amenable to immunotherapeutic intervention.