Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells.
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.
Oh
SangKon
S
Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1578, USA.
Terabe
Masaki
M
Pendleton
C David
CD
Bhattacharyya
Anu
A
Bera
Tapan K
TK
Epel
Malka
M
Reiter
Yoram
Y
Phillips
John
J
Linehan
W Marston
WM
Kasten-Sportes
Claude
C
Pastan
Ira
I
Berzofsky
Jay A
JA
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*
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D009687:Nuclear Proteins; D010446:Peptide Fragments; C413185:TARP