Expression of tumor rejection antigens in colorectal carcinomas

Expression of tumor rejection antigens in colorectal carcinomas
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DOI:
10.1002/cncr.10421
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发表时间:
2002-03-15
期刊:
影响因子:
6.2
通讯作者:
Shirouzu, K
Shirouzu, K
中科院分区:
医学1区
文献类型:
--
作者:
Sasatomi, T;Suefuji, Y;Shirouzu, K

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背景作者最近报道,SART 2和SART 3抗原编码由HLA-A24限制性和肿瘤特异性细胞毒性T淋巴细胞(CTL)识别的肿瘤表位,所述细胞毒性T淋巴细胞(CTL)建立自食管癌患者。本研究旨在通过对这些抗原的研究,为大肠癌患者的特异性免疫治疗寻找潜在的分子。用Western blotting检测SART 2和SART 3抗原在大肠癌细胞系和癌组织中的表达。为了诱导CTL,在体外用肽刺激HLA A-24阳性癌症患者的外周血单核细胞(PBMC)。140 kD SART 3抗原在所有6个结肠癌细胞系的胞质和核组分中表达,在41个结肠直肠癌组织样品的胞质组分中有27个(65.9%),在41个核组分中有30个(73.2%),在7个非肿瘤组织中没有表达。100 kD的SART 2抗原表达在2的6个结肠癌细胞系,5的20个(25%)结直肠癌组织样品的细胞质组分的细胞质组分,并在0的7个非肿瘤组织。用SART 3的两个免疫原性肽段刺激结肠癌患者的PBMC,可诱导出HLA-A24限制性CTL。SART 3抗原可作为大肠癌特异性免疫治疗的靶分子。(C)2002年美国癌症协会
BACKGROUND. The authors recently reported that the SART2 and SART3 antigens encode tumor epitopes recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs) established from esophageal carcinoma patients. The current study investigated these antigens to explore a potential molecule for specific immunotherapy for colorectal carcinoma patients.METHODS. The SART2 and SART3 antigens were investigated by Western blotting in colorectal carcinoma cell lines and in cancer tissues. For induction of CTLs, peripheral blood mononuclear cells (PBMCs) of HLA A-24-positive cancer patients were stimulated in vitro with peptides.RESULTS. The 140 kD SART3 antigen was expressed in both the cytosol and nuclear fractions of all six colon carcinoma cell lines, 27 of 41 (65.9%) cytosol fractions, 30 of 41 (73.2%) nuclear fractions of colorectal carcinoma tissue samples, and in 0 of 7 non-tumorous tissues. The 100 kD SART2 antigen was expressed in the cytosol fractions of 2 of 6 colon carcinoma cell lines, 5 of 20 (25%) cytosol fractions of colorectal carcinoma tissue samples, and in 0 of 7 non tumorous tissues. HLA-A24-restricted CTLs cytotoxic to colon carcinoma cells were induced from PBMCs of colon carcinoma patients by stimulation with the two immunogenic peptides of SART3.CONCLUSIONS. The SART3 antigen could be an appropriate target molecule for specific immunotherapy for colorectal carcinoma patients. (C) 2002 American Cancer Society