Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer.
Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer.
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DOI：
10.1186/1479-5876-9-191
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发表时间：
2011-11-05
影响因子：
7.4
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Hayashi S;Kumai T;Matsuda Y;Aoki N;Sato K;Kimura S;Kitada M;Tateno M;Celis E;Kobayashi H
T细胞免疫治疗肺癌(LC)是一种很有前途的新的治疗方法。前列腺六跨膜上皮抗原(STEAP)和ZAST同源多梳状蛋白增强子2(EZH2)在LC中高表达，由于其在正常组织中的表达明显低于肿瘤细胞，这些蛋白被认为是潜在的肿瘤相关抗原(TAAs)，可用于T细胞免疫治疗。我们评估了来自Steap和EZH2的预测的CD4T细胞表位诱导LC细胞株产生抗肿瘤免疫反应的能力。在预测的几个表位中，两个合成肽STEAP281-296和EZH295-109能够有效地诱导受HLA-DR1、DR15或DR53分子限制的CD4T细胞反应，表明这些多肽具有混杂T细胞表位的功能。此外，STEAP281-296和EZH295-109反应性T细胞能够以一种限制的方式直接识别表达STEAP或EZH2的LC细胞。此外，一些Steap反应性T细胞对自体树突状细胞呈递的Steap+肿瘤细胞裂解物有反应。最重要的是，这两种多肽都能够在体外刺激LC患者的T细胞反应。STEAP281-296和EZH295-109是一种强大的CD4T细胞表位，可诱导针对表达STEAP或EZH2的LC产生有效的抗肿瘤T细胞反应。这些观察结果可能有助于将T细胞免疫疗法应用于LC的临床治疗。
T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy. We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines. Out of several predicted epitopes, two synthetic peptides, STEAP281-296 and EZH295-109, were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP281-296 and EZH295-109-reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating in vitro T-cell responses in patients with LC. Peptides STEAP281-296 and EZH295-109 function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC.
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DOI：
10.1158/1078-0432.ccr-08-1013
发表时间：
2008-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Ougolkov AV;Bilim VN;Billadeau DD
通讯作者：
Billadeau DD
DOI：
10.1073/pnas.96.25.14523
发表时间：
1999-12-07
影响因子：
11.1
作者：
Hubert, RS;Vivanco, I;Afar, DEH
通讯作者：
Afar, DEH
影响因子：
11.2
作者：
Kobayashi, Hiroya;Nagato, Toshihiro;Celis, Esteban
通讯作者：
Celis, Esteban
影响因子：
20.4
作者：
Douillard, Jean-Yves;Tribodet, Helene;Pignon, Jean Pierre
通讯作者：
Pignon, Jean Pierre
影响因子：
5.8
作者：
Alves, Pedro M. S.;Faure, Olivier;Kosmatopoulos, Kostas
通讯作者：
Kosmatopoulos, Kostas