Generation of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer.

Abstract

To identify potential immunogenic peptides derived from CA125. A bioinformatics approach was used to identify peptides derived from CA125 that bind to human leukocyte antigen A2.1 and elicit peptide-specific human cytotoxic T-lymphocyte responses in healthy individuals and patients with ovarian carcinoma. CD8+ cytotoxic T-lymphocyte populations generated against 4 CA125-derived peptides were able to induce lysis of autologous peptide-loaded target cells. CA125 YTLDrDSLYV peptide-specific cytotoxic T lymphocytes were found to effectively kill ovarian tumors expressing CA125. Cytotoxicity was inhibited by antihuman leukocyte antigen A2.1 (BB7-2) and antihuman leukocyte antigen class I (W6/32) antibodies, whereas natural killer-sensitive targets were not lysed. YTLDrDSLYV peptide-specific cytotoxic T lymphocyte precursor frequency was low in peripheral blood leukocytes of normal donors and patients with ovarian cancer as determined by interferon-gamma production in ELISPOT assays. Intracellular cytokine expression measured by flow cytometry showed a type 1 cytokine profile in YTLDrDSLYV peptide-specific cytotoxic T lymphocytes. The CA125 YTLDrDSLYV peptide is an immunogenic epitope and may represent an attractive target for immunotherapy of ovarian cancer.