Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells

• Published in: Cancer research (Chicago, Ill.) Vol. 64; no. 7; pp. 2610 - 2618
• Main Authors: OH, Sangkon, TERABE, Masaki, PASTAN, Ira, BERZOFSKY, Jay A, PENDLETON, C. David, BHATTACHARYYA, Anu, BERA, Tapan K, EPEL, Malka, REITER, Yoram, PHILLIPS, John, LINEHAN, W. Marston, KASTEN-SPORTES, Claude
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-04-2004
• Subjects: Amino Acid Sequence; Animals; Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - immunology; Breast Neoplasms - therapy; Cancer Vaccines - immunology; Epitopes, T-Lymphocyte - immunology; Female; HLA-A2 Antigen - immunology; HLA-A2 Antigen - metabolism; Humans; Lymphocyte Activation - immunology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Nuclear Proteins - immunology; Peptide Fragments - immunology; Peptide Fragments - metabolism; Pharmacology. Drug treatments; Prostatic Neoplasms - immunology; Prostatic Neoplasms - therapy; T-Lymphocytes, Cytotoxic - immunology; Tumors; Human; Antigenic determinant; T-Lymphocyte; Cytotoxicity; Mammary gland; Wild type; Urogenital system; Cytotoxic T lymphocyte; Prostate
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-03-2183

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 gamma 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.