Antitumor effect of antibody against a SEREX-defined antigen (UOEH-LC-1) on lung cancer xenotransplanted into severe combined immunodeficiency mice.
Antitumor effect of antibody against a SEREX-defined antigen (UOEH-LC-1) on lung cancer xenotransplanted into severe combined immunodeficiency mice.
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DOI：
10.1158/0008-5472.can-06-3889
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发表时间：
2007-09
期刊：
影响因子：
11.2
通讯作者：
Makiko Mizukami;T. Hanagiri;M. Yasuda;K. Kuroda;Y. Shigematsu;T. Baba;Takashi Fukuyama;Y. Nagata
中科院分区：
文献类型：
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作者：
Makiko Mizukami;T. Hanagiri;M. Yasuda;K. Kuroda;Y. Shigematsu;T. Baba;Takashi Fukuyama;Y. Nagata
我们先前报道了肺癌患者肿瘤浸润B淋巴细胞的体液免疫应答和22个编码肿瘤相关抗原的基因，通过重组表达克隆方法进行抗原血清学鉴定。在这项研究中，我们调查了这些基因之一，指定大学的职业和环境卫生-肺癌抗原-1（UOEH-LC-1），它具有一个胞外结构域。定量逆转录PCR显示UOEH-LC-1在正常组织中广泛表达。然而，与配对的正常肺组织相比，它在11个肺癌细胞系中的5个（45.5%）和15个肺癌组织中的9个（60%）中过表达。序列分析表明UOEH-LC-1具有跨膜结构域。使用针对UOEH-LC-1的多克隆抗体的流式细胞术分析显示，在UOEH-LC-1 mRNA表达阳性的肺癌细胞系上呈阳性染色。噬菌斑试验显示抗UOEH-LC-1抗体对来自抗原编码噬菌体的UOEH-LC-1蛋白具有特异性反应性。用抗UOEH-LC-1抗体进行免疫组化染色，28例肺癌标本中有7例（25.0%）细胞表面呈阳性染色。施用抗UOEH-LC-1抗体抑制异种移植到严重联合免疫缺陷小鼠中的UOEH-LC-1阳性肿瘤的生长。补体依赖性细胞毒作用是其抑制肿瘤生长的机制之一。这些结果表明，抗UOEH-LC-1的抗体因此似乎具有作为肺癌治疗的有希望的治疗潜力。
We previously reported the humoral immune response of tumor-infiltrating B lymphocytes in a lung cancer patient and 22 genes coding tumor-associated antigens identified using the serological identification of antigens by recombinant expression cloning method. In this study, we investigated one of these genes, designated University of Occupational and Environmental Health-Lung cancer antigen-1 (UOEH-LC-1), which has an extracellular domain. Quantitative reverse transcription-PCR revealed that UOEH-LC-1 was expressed ubiquitously in the normal tissues tested. However, it was overexpressed in 5 of 11 (45.5%) lung cancer cell lines and also in 9 of 15 (60%) lung cancer tissues compared with the paired normal lung tissues. A sequence analysis revealed that UOEH-LC-1 has a transmembrane domain. Flow cytometry analysis using a polyclonal antibody against UOEH-LC-1 revealed positive staining on lung cancer cell lines that were positive for expression of mRNA of UOEH-LC-1. Phage plaque assay showed the specific reactivity of anti-UOEH-LC-1 antibody against UOEH-LC-1 protein derived from the antigen encoding phage. By immunohistochemical staining with the anti-UOEH-LC-1 antibody, 7 of 28 (25.0%) lung cancer specimens showed positive staining on the cell surface. The administration of anti-UOEH-LC-1 antibody inhibited the growth of the UOEH-LC-1-positive tumors that were xenotransplanted into severe combined immunodeficiency mice. Complement-dependent cytotoxicity was one of the mechanisms to suppress the tumor growth. These results suggest that the antibody against UOEH-LC-1 therefore seems to have a promising therapeutic potential as a treatment for lung cancer.