The humanized anti-HM1.24 antibody effectively kills multiple myeloma cells by human effector cell-mediated cytotoxicity

The humanized anti-HM1.24 antibody effectively kills multiple myeloma cells by human effector cell-mediated cytotoxicity
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DOI:
10.1016/s0161-5890(99)00029-2
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发表时间:
1999-04-01
影响因子:
3.6
通讯作者:
Tsuchiya, M
Tsuchiya, M
中科院分区:
医学3区
文献类型:
--
作者:
Ono, K;Ohtomo, T;Tsuchiya, M

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一种小鼠单克隆抗体,抗hm1.24 (IgG2a/kappa),结合在多发性骨髓瘤(MM)细胞上优先过表达的表面抗原,并通过抗体依赖细胞介导的细胞毒性(ADCC)对MM细胞表现出有效的抗肿瘤活性。为了开发一种基于抗体的MM免疫疗法,我们利用杂交可变区和两步设计方法成功构建了一种人源化抗hm1.24抗体,其中所有的FRs都与自然加工的人FRs相对应。这种人源化抗hm1.24抗体(IgG1/kappa)能够在人pbmc存在的情况下有效诱导ADCC对抗人骨髓瘤KPMM2和ARH77细胞,其效果与嵌合抗hm1.24抗体一样有效。因此,人源化抗hm1.24抗体有望成为MM患者的有效免疫治疗剂。1999爱思唯尔科学有限公司版权所有。
A mouse monoclonal antibody, anti-HM1.24 (IgG2a/kappa), binds to a surface antigen preferentially overexpressed on multiple myeloma (MM) cells, and exhibits potent antitumor cell activity against MM cells by antibody-dependent cell-mediated cytotoxicity (ADCC). To develop an antibody-based immunotherapy against MM, a humanized anti-HM1.24 antibody, in which all FRs correspond to naturally processed human FRs, has been successfully constructed with the aid of both the hybrid variable region and two-step design methods. This humanized anti-HM1.24 antibody (IgG1/kappa) is able to effectively induce ADCC against human myeloma KPMM2 and ARH77 cells in the presence of human PBMCs as effectively as a chimeric anti-HM1.24 antibody. The humanized anti-HM1.24 antibody, therefore, could be expected as a potent immunotherapeutic agent for MM patients. (C) 1999 Elsevier Science Ltd. All rights reserved.