Chimeric and humanized anti-HM1.24 antibodies mediate antibody-dependent cellular cytotoxicity against lung cancer cells
Chimeric and humanized anti-HM1.24 antibodies mediate antibody-dependent cellular cytotoxicity against lung cancer cells
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DOI：
10.1016/j.lungcan.2008.04.009
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发表时间：
2009-01-01
期刊：
影响因子：
5.3
通讯作者：
Sone, Saburo
中科院分区：
文献类型：
--
作者：
Wang, Wei;Nishioka, Yasuhiko;Sone, Saburo
HM1.24抗原（CD 317）最初被鉴定为在多发性骨髓瘤细胞上优先过表达的细胞表面蛋白。使用抗HM 1.24抗体的免疫治疗已在多发性骨髓瘤患者中进行，作为I期研究。本研究旨在评价鼠-人嵌合抗HM 1.24单克隆抗体和人源化抗HM 1.24单克隆抗体对肺癌细胞的体外抗肿瘤活性。使用从单核细胞（PBMC）分离的人外周血淋巴细胞和单核细胞作为效应细胞。铬释放法测定嵌合和人源化抗HM 1.24单抗对肺癌细胞的抗体依赖性细胞毒作用（ADCC）和补体依赖性细胞毒作用（CDC）。在一些实验中，用各种细胞因子预处理靶细胞或效应细胞。嵌合和人源化抗HM 1.24 mAb有效地诱导针对肺癌细胞的ADCC，其由淋巴细胞介导的效率高于单核细胞。细胞毒活性与肺癌细胞表面HM 1.24表达水平相关。抗HM 1.24 mAb介导的ADCC中，自然杀伤细胞是主要的效应细胞。用IL-2、IL-12、IL-15、M-CSF或IFN-γ处理淋巴细胞或单核细胞显著增加ADCC活性。此外，与IFN-β或IFN-γ培养的肺癌细胞增加了它们对ADCC和CDC的易感性。来自肺癌患者的PBMC诱导的ADCC水平与来自健康供体的PBMC诱导的ADCC水平相当。嵌合或人源化抗HM 7.24单克隆抗体具有作为肺癌新治疗工具的潜力，并且与白细胞介素和干扰素组合可用于增强ADCC。(c)2008爱思唯尔爱尔兰有限公司保留所有权利。
HM1.24 antigen (CD317) was originally identified as a cell surface protein that is preferentially overexpressed on multiple myeloma cells. Immunotherapy using anti-HM1.24 antibody has been performed in patients with multiple myeloma as a phase I study. The aim of this study was to evaluate the antitumor activity of mouse-human chimeric and humanized anti-HM1.24 monoclonal antibodies (mAbs) against lung cancer cells in vitro. Human peripheral blood lymphocytes and monocytes separated from mononuclear cells (PBMCs) were used as effector cells. Antibody-dependent cellular cytotoxicity, (ADCC) and complement-dependent cytotoxicity (CDC) of chimeric and humanized anti-HM1.24 mAbs against lung cancer cells were determined by chromium-release assay. In some experiments, target or effector cells were pretreated with various cytokines. Chimeric and humanized anti-HM1.24 mAbs effectively induced ADCC against lung cancer cells mediated more efficiently by lymphocytes than monocytes. The cytotoxic activity correlated with the level of HM1.24 expression on lung cancer cells. Natural killer cells were identified as the major effector cells in ADCC mediated by the anti-HM1.24 mAb. The treatment of lymphocytes or monocytes with IL-2, IL-12, IL-15, M-CSF, or IFN-gamma significantly increased the ADCC activity. Moreover, the culture of lung cancer cells with IFN-beta or IFN-gamma augmented their susceptibility to ADCC and CDC. PBMCs from patients with lung cancer induced a level of ADCC comparable to that induced by PBMCs from healthy donors. Chimeric or humanized anti-HM7.24 mAbs have potential as a new therapeutic tool in lung cancer, and in combination with interleukins and interferons, could be useful for enhancing ADCC. (c) 2008 Elsevier Ireland Ltd. All rights reserved.