title: Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells.
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 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.
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1578, USA.
authors.forename: SangKon
authors.initials: S
authors.lastname: Oh
authors.forename: Masaki
authors.initials: M
authors.lastname: Terabe
authors.forename: C David
authors.initials: CD
authors.lastname: Pendleton
authors.forename: Anu
authors.initials: A
authors.lastname: Bhattacharyya
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Bera
authors.forename: Malka
authors.initials: M
authors.lastname: Epel
authors.forename: Yoram
authors.initials: Y
authors.lastname: Reiter
authors.forename: John
authors.initials: J
authors.lastname: Phillips
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Claude
authors.initials: C
authors.lastname: Kasten-Sportes
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000628:therapy; D019496:Cancer Vaccines / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D009687:Nuclear Proteins; D010446:Peptide Fragments; C413185:TARP