Kawagoe N, Shintaku I, Yutani S, Etoh H, Matuoka K, Noda S, Itoh K
Department of Immunology, Kurume University School of Medicine, Kurume, Japan.
J Urol. 2000 Dec;164(6):2090-5.
We recently reported that SART3 tumor rejection antigen is recognized by HLA class I restricted cytotoxic T lymphocytes from patients with esophageal cancer. We now investigate the expression of SART3 antigen in renal cell carcinoma to identify an appropriate molecule that may be used in specific immunotherapy of renal cell carcinoma.
Renal cell carcinoma and nontumorous kidney tissues were obtained at surgery. A section of each sample was minced with scissors and stored at -80C until use. SART3 antigen expression was examined in uncultured renal cell carcinoma and nontumorous kidney tissues. We also evaluated the ability of derived peptides to include cytotoxic T lymphocytes in peripheral blood mononuclear cells from patients with renal cell carcinoma.
The SART3 antigen was detected in all renal cell carcinoma cell lines, primary cultures of renal cell carcinoma and nontumorous kidney tissues, and in the cytosol of 57% and 15% of renal cell carcinoma and nontumorous kidney tissues, respectively. HLA-A2402 restricted and tumor specific cytotoxic T lymphocytes (KE4) used in cloning of the SART3 gene were significantly cytotoxic to cells from renal cell carcinoma cell lines and primary cultures of renal cell carcinoma tissue but they did not lyse normal cells, including those from primary cultures of nontumorous kidney tissue. The SART3 peptides derived from positions 109-118 and 315-323 induced HLA-A24 restricted cytotoxic T lymphocytes to renal cell carcinoma cells from peripheral blood mononuclear cells of patients with renal cell carcinoma.
The SART3 antigen and derived peptides may be applied to the specific immunotherapy of HLA-A24+ renal cell carcinoma.
我们最近报道，SART3肿瘤排斥抗原可被来自食管癌患者的HLA I类限制性细胞毒性T淋巴细胞识别。我们现在研究SART3抗原在肾细胞癌中的表达，以确定一种可用于肾细胞癌特异性免疫治疗的合适分子。
手术时获取肾细胞癌和非肿瘤性肾组织。每个样本的一部分用剪刀切碎，储存在-80°C直至使用。在未经培养的肾细胞癌和非肿瘤性肾组织中检测SART3抗原表达。我们还评估了衍生肽诱导肾细胞癌患者外周血单个核细胞中细胞毒性T淋巴细胞的能力。
在所有肾细胞癌细胞系、肾细胞癌原代培养物和非肿瘤性肾组织中均检测到SART3抗原，分别在57%和15%的肾细胞癌和非肿瘤性肾组织的细胞质中检测到。用于克隆SART3基因的HLA-A2402限制性肿瘤特异性细胞毒性T淋巴细胞（KE4）对肾细胞癌细胞系和肾细胞癌组织原代培养物中的细胞具有显著的细胞毒性，但它们不裂解正常细胞，包括非肿瘤性肾组织原代培养物中的细胞。来自第109-118位和315-323位的SART3肽可诱导肾细胞癌患者外周血单个核细胞中的HLA-A24限制性细胞毒性T淋巴细胞作用于肾细胞癌细胞。
SART3抗原及其衍生肽可应用于HLA-A24+肾细胞癌的特异性免疫治疗。
