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

Sang Kon Oh, Masaki Terabe, C. David Pendleton, Anu Bhattacharyya, Tapan K. Bera, Malka Epel, Yoram Reiter, John Phillips, W. Marston Linehan, Claude Kasten-Sportes, Ira Pastan, Jay A. Berzofsky

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

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 γ 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 A2Kb 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.

Original languageEnglish (US)
Pages (from-to)2610-2618
Number of pages9
JournalCancer research
Volume64
Issue number7
DOIs
StatePublished - Apr 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Oh, S. K., Terabe, M., Pendleton, C. D., Bhattacharyya, A., Bera, T. K., Epel, M., Reiter, Y., Phillips, J., Linehan, W. M., Kasten-Sportes, C., Pastan, I., & Berzofsky, J. A. (2004). Human CTLs to Wild-Type and Enhanced Epitopes of a Novel Prostate and Breast Tumor-Associated Protein, TARP, Lyse Human Breast Cancer Cells. Cancer research, 64(7), 2610-2618. https://doi.org/10.1158/0008-5472.CAN-03-2183