BIOLOGICAL-ACTIVITY OF HUMAN MOUSE IGG1, IGG2, IGG3, AND IGG4 CHIMERIC MONOCLONAL-ANTIBODIES WITH ANTITUMOR SPECIFICITY
BIOLOGICAL-ACTIVITY OF HUMAN MOUSE IGG1, IGG2, IGG3, AND IGG4 CHIMERIC MONOCLONAL-ANTIBODIES WITH ANTITUMOR SPECIFICITY
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DOI：
10.1073/pnas.85.13.4852
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发表时间：
1988-07-01
影响因子：
11.1
通讯作者：
KOPROWSKI, H
中科院分区：
文献类型：
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作者：
STEPLEWSKI, Z;SUN, LK;KOPROWSKI, H
构建嵌合抗体，其中抗结肠直肠癌单克隆抗体CO 17 -1A的鼠可变区与人γ 1、γ 2、γ 3和γ 4恒定区连接。在抗体依赖性细胞介导的细胞毒性（ADCC）试验中，比较人-小鼠嵌合蛋白与亲本鼠IgG 2a抗体CO 17 -1A参与人和鼠效应细胞破坏肿瘤细胞的能力。所有嵌合抗体均显示出与人淋巴细胞、单核细胞和粒细胞以及与鼠巨噬细胞的不同程度的ADCC。单核细胞和巨噬细胞能够利用嵌合IgG 1，并在较小程度上，IgG 4和IgG 3抗体裂解肿瘤细胞靶在ADCC测定。嵌合IgG 1和IgG 4抗体在抑制裸鼠肿瘤生长方面几乎与亲本CO 17 -1A抗体一样有效。这些数据表明嵌合IgG 1抗体在其抗肿瘤活性方面是上级的。
Chimeric antibodies were constructed in which the murine variable region of anti-colorectal cancer monoclonal antibody CO17-1A was joined with human .gamma.1, .gamma.2, .gamma.3, and .gamma.4 constant regions. Human-mouse chimeric proteins were compared with the parental murine IgG2a antibody CO17-1A for their ability to participate in tumor-cell destruction by human and murine effector cells in antibody-dependent cell-mediated cytotoxicity (ADCC) assays. All of the chimeric antibodies showed different degrees of ADCC with human lymphocytes, monocytes, and granulocytes and with murine macrophages. Monocytes and macrophages were able to utilize the chimeric IgG1 and, to a lesser degree, IgG4 and IgG3 antibodies to lyse tumor-cell targets in ADCC assays. The chimeric IgG1 and IgG4 antibodies were nearly as effective as the parental CO17-1A antibody in inhibiting tumor growth in nude mice. These data indicate that chimeric IgG1 antibody is superior in its antitumor activity.