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Human CTLs to Wild-Type and Enhanced Epitopes of a Novel Prostate and Breast Tumor-Associated Protein, TARP, Lyse Human Breast Cancer Cells

¹ Vaccine Branch, ² Laboratory of Molecular Biology, ³ Urologic Oncology Branch, and ⁴ Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; ⁵ Technion-Israel Institute of Technology, Technion City, Haifa, Israel; and ⁶ Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Vaccine therapy for prostate and breast cancer may have potential for treating these major causes of death in males and females, respectively. Critical to the development of tumor-specific vaccines is finding and characterizing novel antigens to be recognized by CD8⁺ T cells. To define new CD8⁺ T-cell tumor antigens, we determined two wild-type HLA-A2 epitopes from a recently found tumor-associated protein, TARP (T-cell receptor alternate reading frame protein), expressed in prostate and breast cancer cells. We were also able to engineer epitope-enhanced peptides by sequence modifications. Both wild-type and enhanced epitopes induced peptide-specific CD8⁺ T-cell responses in A2K^b transgenic mice. In vitro restimulation of human CD8⁺ T cells from a prostate cancer patient resulted in CD8⁺ T cells reactive to the peptide epitopes that could lyse HLA-A2⁺ human breast cancer cells (MCF-7) expressing TARP. Epitope-specific human CD8⁺ T cells were also enumerated in patients’ peripheral blood by tetramer staining. Our data suggest that HLA-A2-binding TARP epitopes and enhanced epitopes discovered in this study could be incorporated into a potential vaccine for both breast and prostate cancer.

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