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Induction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells

From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, the Department of Microbiology and Immunology, and the Division of Gynecologic Oncology, University of Arkansas, Little Rock, Arkansas; and the Division of Gynecologic Oncology, University of Brescia, Brescia, Italy.

Address reprint requests to: Alessandro D. Santin, MD University of Arkansas UAMS Medical Center Division of Gynecologic Oncology 4301 West Markham Little Rock, AR 72205-7199

Objective: To evaluate the potential of dendritic cells pulsed with acid-eluted peptides derived from autologous ovarian cancer cells for eliciting a tumor-specific cytotoxic T cell response in women with advanced ovarian cancer.

Methods: CD8+ T lymphocytes derived from peripheral blood mononuclear cells stimulated in vitro with autologous ovarian tumor peptide-pulsed dendritic cells were tested for their ability to induce an HLA class I–restricted cytotoxic T lymphocyte response against autologous tumor cells. To correlate cytotoxic activity by cytotoxic T lymphocytes with T cell phenotype, we used two-color flow cytometric analysis of surface markers and intracellular cytokine expression (interferon- versus interleukin-4).

Results: CD8+ cytotoxic T lymphocyte responses against autologous ovarian tumor cells were elicited in three consecutive women who had advanced ovarian cancer. Although cytotoxic T lymphocyte populations from all women expressed strong cytolytic activity against autologous tumor cells, they did not lyse autologous lymphoblasts or Epstein-Barr virus-transformed cell lines, and they showed negligible cytotoxicity against the natural killer-sensitive cell line K-562. Cytotoxicity against the autologous tumor cells was significantly inhibited by anti-HLA class I (W6/32) and anti-HLA-A2 (BB7-2) monoclonal antibodies. CD8+ cytotoxic T lymphocytes expressed variable levels of CD56 and preferentially expressed interferon- rather than interleukin-4.

Conclusions: Peptide-pulsed dendritic cells induced specific CD8+ cytotoxic T lymphocytes that killed autologous tumor cells from women with advanced ovarian cancer. This finding might contribute to the development of active or adoptive immunotherapy for residual or resistant ovarian cancer after standard surgery and cytotoxic treatment.

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