CHIMERIC HUMAN-ANTIBODY MOLECULES - MOUSE ANTIGEN-BINDING DOMAINS WITH HUMAN CONSTANT REGION DOMAINS
CHIMERIC HUMAN-ANTIBODY MOLECULES - MOUSE ANTIGEN-BINDING DOMAINS WITH HUMAN CONSTANT REGION DOMAINS
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DOI：
10.1073/pnas.81.21.6851
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
OI, VT
中科院分区：
文献类型：
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作者：
MORRISON, SL;JOHNSON, MJ;OI, VT
通过获取具有已知抗原结合特异性的小鼠抗体产生骨髓瘤细胞系的可变区基因，并使用重组DNA技术将其连接至人IG恒定区基因，产生具有确定抗原结合特异性的小鼠-人抗体分子。构建嵌合基因，其利用来自骨髓瘤细胞系S107的重排和表达的抗原结合可变区外显子，所述骨髓瘤细胞系S107产生伊加（κ）抗磷酸胆碱抗体将H链可变区外显子与人IgG 1或IgG 2 H链恒定区基因连接，将来自同一骨髓瘤的L链可变区外显子与人κ连接。L链基因。将这些基因转染到小鼠骨髓瘤细胞系中，产生产生嵌合小鼠-人IgG（κ）的转化细胞。或伊加（κ）抗磷酸胆碱抗体转化的细胞系在小鼠中保持致瘤性，并且嵌合分子存在于荷瘤小鼠的腹水和血清中。
Mouse-human antibody molecules of defined antigen-binding specificity were created by taking the variable region genes of a mouse antibody-producing myeloma cell line with known antigen-binding specificity and joining them to human Ig constant region genes using recombinant DNA techniques. Chimeric genes were constructed that utilized the rearranged and expressed antigen-binding variable region exons from the myeloma cell line S107, which produces an IgA (.kappa.) anti-phosphocholine antibody. The H chain variable region exon was joined to human IgG1 or IgG2 H chain constant region genes, and the L chain variable region exon from the same myeloma was joined to the human .kappa. L chain gene. These genes were transfected into mouse myeloma cell lines, generating transformed cells that produce chimeric mouse-human IgG (.kappa.) or IgA (.kappa.) anti-phosphocholine antibodies. The transformed cell lines remained tumorigenic in mice and the chimeric molecules were present in the ascitic fluids and sera of tumor-bearing mice.