Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors
Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors
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DOI：
10.1158/1078-0432.ccr-07-0110
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发表时间：
2007-07-15
影响因子：
11.5
通讯作者：
Morimoto, Chikao
中科院分区：
文献类型：
--
作者：
Inamoto, Teruo;Yamada, Taketo;Morimoto, Chikao
目的：CD26 是一种 110 kDa 的细胞表面抗原，在肿瘤发展中发挥作用。在本报告中，我们表明CD26在恶性间皮瘤的细胞表面高表达，并且新开发的人源化抗CD26单克隆抗体（mAb）在体外和体内实验中对恶性间皮瘤细胞具有抑制作用。 实验设计：使用免疫组织化学方法，对12名患者的手术标本进行了7种恶性间皮瘤的检测。 评估了间皮瘤、三种反应性间皮细胞和两种腺瘤样肿瘤的 CD26 表达。在转染 CD26 表达质粒、人源化抗 CD26 mAb 或抗 CD26 小干扰 RNA 的情况下评估 CD26 对恶性间皮瘤细胞的影响。在人恶性间皮瘤细胞小鼠异种移植模型中评估人源化抗 CD26 mAb 的体内生长抑制作用。结果：在手术标本中，CD26 在恶性间皮瘤中高表达，但在良性间皮组织中不表达。小干扰 RNA 耗尽 CD26 会导致粘附特性丧失，表明 CD26 是细胞外基质的结合蛋白。此外，我们的体外数据表明，人源化抗 CD26 mAb 除了通过 p27(kip1) 积累产生直接抗肿瘤作用外，还通过抗体依赖性细胞介导的细胞毒性诱导恶性间皮瘤细胞裂解。涉及人类恶性间皮瘤细胞的小鼠异种移植模型的体内实验表明，人源化抗 CD26 mAb 治疗可显着抑制荷瘤小鼠的肿瘤生长，从而提高生存率。结论：我们的数据强烈表明，人源化抗 CD26 mAb 治疗可能具有潜在的临床用途，可作为 CD26 阳性恶性间皮瘤的新型癌症治疗剂。 间皮瘤。
Purpose: CD26 is a 110-kDa cell surface antigen with a role in tumor development. In this report, we show that CD26 is highly expressed on the cell surface of malignant mesothelioma and that a newly developed humanized anti-CD26 monoclonal antibody (mAb) has an inhibitory effect on malignant mesothelioma cells in both in vitro and in vivo experiments.Experimental Design: Using immunohistochemistry, 12 patients surgical specimens consisting of seven malignant mesothelioma, three reactive mesothelial cells, and two adenomatoid tumors were evaluated for expression of CD26. The effects of CD26 on malignant mesothelioma cells were assessed in the presence of transfection of CD26-expressing plasmid, humanized anti-CD26 mAb, or small interfering RNA against CD26. The in vivo growth inhibitory effect of humanized anti-CD26 mAb was assessed in human malignant mesothelioma cell mouse xenograft models.Results: In surgical specimens, CD26 is highly expressed in malignant mesothelioma but not in benign mesothelial tissues. Depletion of CD26 by small interfering RNA results in the loss of adhesive property, suggesting that CD26 is a binding protein to the extracellular matrix. Moreover, our in vitro data indicate that humanized anti-CD26 mAb induces cell lysis of malignant mesothelioma cells via antibody-dependent cell-mediated cytotoxicity in addition to its direct anti-tumor effect via p27(kip1) accumulation. In vivo experiments with mouse xenograft models involving human malignant mesothelioma cells show that humanized anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival.Conclusions: Our data strongly suggest that humanized anti-CD26 mAb treatment may have potential clinical use as a novel cancer therapeutic agent in CD26-positive malignant mesothelioma.