Recognition of prostate and melanoma tumor cells by six-transmembrane epithelial antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen class II-restricted manner
Recognition of prostate and melanoma tumor cells by six-transmembrane epithelial antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen class II-restricted manner
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DOI：
10.1158/0008-5472.can-07-0304
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发表时间：
2007-06-01
期刊：
影响因子：
11.2
通讯作者：
Celis, Esteban
中科院分区：
文献类型：
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作者：
Kobayashi, Hiroya;Nagato, Toshihiro;Celis, Esteban
前列腺六跨膜上皮抗原（STEAP）蛋白是T细胞免疫治疗的一个有吸引力的候选者，因为它在前列腺癌和各种其他肿瘤类型中过表达。已经描述了几种能够刺激ctl杀死表达steap的肿瘤细胞的肽表位。我们的目标是鉴定STEAP的辅助性T淋巴细胞（HTL）表位，以优化针对表达STEAP的恶性肿瘤的T细胞免疫疗法。使用HLA ii类结合肽的计算机算法预测STEAP的候选HTL表位，并通过健康个体和前列腺癌患者CD4 T淋巴细胞的体外肽疫苗接种来测试其引发HTL反应的能力。两种肽（STEAP（102-116）和STEAP(192-206)）在正常个体和前列腺癌患者中均能有效刺激体外抗肿瘤HTL反应。值得注意的是，两种STEAP HTL肽都表现为混杂的T细胞表位，因为它们在一个以上MHC II类等位基因的背景下刺激T细胞。这些新描述的STEAP HTL表位可能对设计和优化针对表达STEAP的肿瘤的T细胞免疫治疗具有价值。
The six-transmembrane epithelial antigen of prostate (STEAP) protein is an attractive candidate for T cell-based immunotherapy because it is overexpressed in prostate cancer and various other tumor types. Several peptide epitopes capable of stimulating CTLs that killed STEAP-expressing tumor cells have been described. Our goal was the identification of helper T lymphocyte (HTL) epitopes of STEAP for the optimization of T cell-based immunotherapies against STEAP-expressing malignancies. Candidate HTL epitopes for STEAP were predicted using in silico algorithms for HLA class II-binding peptides and were tested for their ability to elicit HTL responses by in vitro peptide vaccination of CD4 T lymphocytes from healthy individuals and prostate cancer patients. Two peptides (STEAP(102-116) and STEAP(192-206)) were effective in stimulating in vitro antitumor HTL responses in both normal individuals and prostate cancer patients. Notably, both STEAP HTL peptides behaved as promiscuous T-cell epitopes because they stimulated T cells in the context of more than one MHC class II allele. These newly described STEAP HTL epitopes could be of value for the design and optimization of T cell-based immunotherapy against STEAP-expressing tumors.