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

被引:63
作者
Oh, S
Terabe, M
Pendleton, CD
Bhattacharyya, A
Bera, TK
Epel, M
Reiter, Y
Phillips, J
Linehan, WM
Kasten-Sportes, C
Pastan, I
Berzofsky, JA
机构
[1] NCI, Ctr Canc Res, Vaccine Branch, NIH, Bethesda, MD 20892 USA
[2] NCI, Ctr Canc Res, Mol Biol Lab, NIH, Bethesda, MD 20892 USA
[3] NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA
[4] NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA
[5] Technion Israel Inst Technol, Haifa, Israel
[6] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD USA
关键词
D O I
10.1158/0008-5472.CAN-03-2183
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2610 / 2618
页数:9
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