可介导癌细胞裂解的嵌合型小鼠-人IgG1抗体。
Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells.
作者信息
Liu A Y, Robinson R R, Hellström K E, Murray E D, Chang C P, Hellström I
出版信息
Proc Natl Acad Sci U S A. 1987 May;84(10):3439-43. doi: 10.1073/pnas.84.10.3439.
A chimeric mouse-human antibody has been created that recognizes an antigen found on the surface of cells from many carcinomas. Immunoglobulin constant (C) domains of the mouse monoclonal antibody L6, C gamma 2a and C kappa, were substituted by the human C gamma 1 and C kappa by recombining cDNA modules encoding variable or C domains. The cDNA constructs were transfected into lymphoid cells for antibody production. The chimeric antibody and mouse L6 antibody bound to carcinoma cells with equal affinity and mediated complement-dependent cytolysis. In the presence of human effector cells, the chimeric antibody gave antibody-dependent cellular cytotoxicity at 100 times lower concentration than that needed for the mouse L6 antibody. The chimeric antibody, but not the mouse L6 antibody, is effective against a melanoma line expressing small amounts of the L6 antigen. The findings point to the usefulness of the chimeric antibody approach for obtaining agents with strong antitumor activity for possible therapeutic use in man.
已制备出一种嵌合型小鼠 - 人抗体，该抗体可识别多种癌细胞表面存在的一种抗原。通过重组编码可变区或恒定区的cDNA模块，将小鼠单克隆抗体L6的免疫球蛋白恒定（C）结构域Cγ2a和Cκ替换为人Cγ1和Cκ。将cDNA构建体转染到淋巴细胞中以产生抗体。嵌合抗体和小鼠L6抗体以相同的亲和力与癌细胞结合，并介导补体依赖性细胞溶解。在存在人效应细胞的情况下，嵌合抗体产生抗体依赖性细胞毒性所需的浓度比小鼠L6抗体低100倍。嵌合抗体而非小鼠L6抗体对表达少量L6抗原的黑色素瘤细胞系有效。这些发现表明嵌合抗体方法对于获得具有强大抗肿瘤活性的药物用于人类可能的治疗具有实用性。
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