Induction of human tumor-associated differentially expressed gene-12 (TADG-12/TMPRSS3)-specific cytotoxic T lymphocytes in human lymphocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer.

Tumor-associated differentially expressed gene-12 (TADG-12) is a serine protease recently found highly differentially expressed in epithelial ovarian cancer. The goal of this study was to identify potential immunogenic peptides derived from TADG-12 for immunotherapy of ovarian carcinoma. A bioinformatics approach (ie, the BIMAS algorithm, National Institutes of Health, http://bimas.dcrt.nih.gov/molbio/hla_bind) was used to identify multiple immunogenic peptides derived from TADG-12 that bind to human leukocyte antigen-A2.1 and elicit peptide-specific human cytotoxic T lymphocyte (CTL) responses in healthy individuals and in patients with advanced stage ovarian cancer. CD8+ CTL populations generated against 5 TADG-12-derived peptides were consistently able to induce lysis of autologous peptide-loaded target cells above background. Importantly, TADG-12 YLPKSWTIQV peptide-specific CTLs from healthy donors and ovarian cancer patients were found to effectively kill ovarian cancer cells naturally expressing TADG-12. Cytotoxicity was significantly inhibited by anti-human lymphocyte antigen (HLA)-A2.1 (BB7-2) and anti-HLA class I (W6 of 32) monoclonal antibodies, whereas natural killer-sensitive K562 cells were not lysed. TADG-12 YLPKSWTIQV peptide-specific CTL precursor frequency was low in peripheral blood leukocytes of normal donors and ovarian cancer patients, as determined by interferon-gamma production in enzyme-linked immunosorbent spot-forming cell assays. Intracellular cytokine expression measured by flow cytometry after OKT-3 monoclonal antibody stimulation showed a type 1 cytokine profile in YLPKSWTIQV peptide-specific CTLs. The TADG-12 YLPKSWTIQV peptide is an immunogenic epitope in ovarian tumors and may represent an attractive target for immunotherapy of ovarian cancer. These data may pave the way for TADG-12 peptide-derived cell-based therapy, including dendritic cell immunotherapy, for the vaccination of ovarian cancer patients harboring chemotherapy-resistant or residual disease.

Bellone S ，Anfossi S ，O'Brien TJ ，Cannon MJ ，Silasi DA ，Azodi M ，Schwartz PE ，Rutherford TJ ，Pecorelli S ，Santin AD ... -  《CANCER》

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

Bellone S ，Anfossi S ，O'Brien TJ ，Cannon MJ ，Silasi DA ，Azodi M ，Schwartz PE ，Rutherford TJ ，Pecorelli S ，Santin AD ... -  《-》

Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme.

Bondurant KL ，Crew MD ，Santin AD ，O'Brien TJ ，Cannon MJ ... -  《CLINICAL CANCER RESEARCH》

In vitro induction of tumor-specific human lymphocyte antigen class I-restricted CD8 cytotoxic T lymphocytes by ovarian tumor antigen-pulsed autologous dendritic cells from patients with advanced ovarian cancer.

Santin AD ，Hermonat PL ，Ravaggi A ，Bellone S ，Pecorelli S ，Cannon MJ ，Parham GP ... -  《AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY》

Expression of CD56 by human papillomavirus E7-specific CD8+ cytotoxic T lymphocytes correlates with increased intracellular perforin expression and enhanced cytotoxicity against HLA-A2-matched cervical tumor cells.

Santin AD ，Hermonat PL ，Ravaggi A ，Bellone S ，Roman JJ ，Jayaprabhu S ，Pecorelli S ，Parham GP ，Cannon MJ ... -  《CLINICAL CANCER RESEARCH》