STEAP, a prostate tumor antigen, is a target of human CD8+ T cells
STEAP, a prostate tumor antigen, is a target of human CD8+ T cells
复制标题
DOI：
10.1007/s00262-006-0165-3
复制
发表时间：
2006-12-01
影响因子：
5.8
通讯作者：
Kosmatopoulos, Kostas
中科院分区：
文献类型：
--
作者：
Alves, Pedro M. S.;Faure, Olivier;Kosmatopoulos, Kostas
STEAP 是最近发现的一种蛋白质，显示在前列腺癌中特别过度表达，并且也存在于来自前列腺癌、胰腺癌、结肠癌、乳腺癌、睾丸癌、宫颈癌、膀胱癌和卵巢癌、急性淋巴细胞白血病和尤文肉瘤的许多人类癌细胞系中。这种表达谱使 STEAP 成为广泛癌症免疫治疗的有吸引力的候选者。为了研究STEAP是否是一种可以被特异性CD8+T细胞靶向的肿瘤抗原，我们鉴定了两种高亲和力HLA-A*0201限制肽（STEAP(86-94)和STEAP(262-270)）。这些肽在 HLA-A*0201 转基因 HHD 小鼠体内具有免疫原性。肽特异性鼠 C138 T 细胞可识别与 HHD (HLA-A*0201) 和 STEAP cDNA 构建体共转染的 COS-7 细胞以及 HLA-A*0201 + STEAP + 人肿瘤细胞。此外，STEAP(86-94)和STEAP(262-270)刺激来自HLA-A*0201(+)健康供体的特异性CD8(+)T细胞，并且这些肽特异性CD8(+)T细胞以HLA-A*0201限制的方式识别STEAP阳性人类肿瘤细胞。重要的是，在 NSCLC 和前列腺癌患者的离体外周血单核细胞中检测到了 STEAP(86-94) 特异性 T 细胞并具有反应性。这些结果表明STEAP可以成为抗肿瘤CD8(+)T细胞的靶标，并且STEAP肽可用于广谱肿瘤免疫治疗。
STEAP is a recently identified protein shown to be particularly overexpressed in prostate cancer and also present in numerous human cancer cell lines from prostate, pancreas, colon, breast, testicular, cervical, bladder and ovarian carcinoma, acute lymphocytic leukemia and Ewing sarcoma. This expression profile renders STEAP an appealing candidate for broad cancer immunotherapy. In order to investigate if STEAP is a tumor antigen that can be targeted by specific CD8(+) T cells, we identified two high affinity HLA-A*0201 restricted peptides (STEAP(86-94) and STEAP(262-270)). These peptides were immunogenic in vivo in HLA-A*0201 transgenic HHD mice. Peptide specific murine C138 T cells recognized COS-7 cells co-transfected with HHD (HLA-A*0201) and STEAP cDNA constructs and also HLA-A*0201 + STEAP + human tumor cells. Furthermore, STEAP(86-94) and STEAP(262-270) stimulated specific CD8(+) T cells from HLA-A*0201(+) healthy donors, and these peptide specific CD8(+) T cells recognized STEAP positive human tumor cells in an HLA-A*0201-restricted manner. Importantly, STEAP(86-94)-specific T cells were detected and reactive in the peripheral blood mononuclear cells in NSCLC and prostate cancer patients ex vivo. These results show that STEAP can be a target of anti-tumor CD8(+) T cells and that STEAP peptides can be used for a broad-spectrum-tumor immunotherapy.