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Recognition of Prostate Tumor Cells by Cytotoxic T Lymphocytes Specific for Prostate-specific Membrane Antigen¹

Department of Immunology, Mayo Graduate School, and Mayo Cancer Center, Mayo Clinic, Rochester, Minnesota 55905

The development of immunotherapy for cancer, such as synthetic peptide-based vaccines, relies heavily on the identification of appropriate epitopes capable of eliciting antitumor T-cell responses. We have used a combination of computer-based algorithms to predict peptide sequences from prostate-specific membrane antigen (PSMA) capable of stimulating in vitro CTLs restricted by the HLA-A2 MHC molecule. Four of the five peptides that were predicted by these algorithms were capable of inducing antigen-specific CTLs that killed target cells that were pulsed exogenously with the corresponding peptides. However, only one of the four peptides, PSMA₂₇, induced CTLs that were effective at recognizing prostate tumor cells expressing the HLA-A2 and PSMA molecules. These results underline the importance of demonstrating antitumor reactivity of peptide-induced CTLs for the selection of epitopes destined to become immunotherapeutic for prostate cancer.

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