Shintaku I, Kawagoe N, Yutani S, Hoshi S, Orikasa S, Yoshizumi O, Itoh K
Department of Urology, Tohoku University, School of Medicine, Sendai, Japan.
Urol Res. 2000 Jun;28(3):178-84. doi: 10.1007/s002400000103.
We have previously described the SART1 gene, which encodes both the SART1(259) antigen expressed in the cytosol of the majority of squamous cell carcinomas and some adenocarcinomas and the SART1(800) antigen expressed in the nucleus of the majority of proliferating cells. The SART1(259) antigen is recognized by HLA-A24 and A26-restricted cytotoxic T lymphocytes (CTLs). The present study investigated the expression of these two antigens in renal cell carcinomas (RCCs) in order to identify an appropriate molecule for use in specific immunotherapy for RCC patients. These two antigens were detected in all RCC cell lines and cells of the primary cultures of the RCCs tested. Further, they were detectable in cells of the primary cultures of non-tumorous kidney tissues. In contrast to these cultured cells, SART1(259) was detectable in only a few uncultured RCC tissues (5/20, 25%) and was undetectable in non-tumorous kidney tissues. SART1(800) was also scarcely detectable in uncultured RCC tissues (3/20, 15%) and non-tumorous kidney tissues (4/20, 20%). HLA-A2402-restricted and tumor-specific CTL (KE4-CTL) used for the cloning of the SART1 gene showed significant levels of cytotoxicity to both the cells from the RCC cell line and the cells from the primary cultures of RCC tissues, but did not lyse any normal cells, including cells from the primary cultures of non-tumorous kidney tissues. The SART1-derived peptide at positions 690-698 induced HLA-A24 restricted CTLs cytotoxic to RCC cells from peripheral blood mononuclear cells (PBMCs) of RCC patients. Therefore, the SART1 peptide could be an appropriate molecule for use in peptide-based specific immunotherapy for RCC patients.
我们之前已经描述过SART1基因，它编码两种抗原，即大多数鳞状细胞癌和部分腺癌胞质中表达的SART1(259)抗原，以及大多数增殖细胞核中表达的SART1(800)抗原。SART1(259)抗原可被HLA - A24和A26限制性细胞毒性T淋巴细胞（CTLs）识别。本研究调查了这两种抗原在肾细胞癌（RCCs）中的表达情况，以便确定一种适用于RCC患者特异性免疫治疗的分子。在所有测试的RCC细胞系和RCC原代培养细胞中均检测到了这两种抗原。此外，在非肿瘤性肾组织的原代培养细胞中也可检测到它们。与这些培养细胞不同，SART1(259)仅在少数未培养的RCC组织中可检测到（5/20，25%），而在非肿瘤性肾组织中未检测到。SART1(800)在未培养的RCC组织（3/20，15%）和非肿瘤性肾组织（4/20，20%）中也几乎检测不到。用于克隆SART1基因的HLA - A2402限制性肿瘤特异性CTL（KE4 - CTL）对RCC细胞系的细胞以及RCC组织原代培养的细胞均表现出显著的细胞毒性水平，但不裂解任何正常细胞，包括非肿瘤性肾组织原代培养的细胞。位于690 - 698位的SART1衍生肽可诱导对RCC患者外周血单个核细胞（PBMCs）中RCC细胞具有细胞毒性的HLA - A24限制性CTLs。因此，SART1肽可能是一种适用于RCC患者基于肽的特异性免疫治疗的分子。
