Structural motifs involved in human IgG antibody effector functions

作者: Judith Greenwood , Mike Clark , Herman Waldmann

DOI: 10.1002/EJI.1830230518

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摘要: A humanized IgG antibody to CAMPATH-1 antigen (CDw52) is known be lympholytic both in vitro and vivo. So as improve therapeutic potency through protein engineering strategies, we wish define the structural motifs underlying some of documented differences function between human (h) IgG1 IgG4 forms antibody. By creation heavy chain domain-switch intra-domain recombinant antibodies have established an important role for carboxy-terminal half CH2 domain determining differential behaviour antibody-dependent cytotoxicity (ADCC) complement lysis. If this same region were necessary effector mechanisms that operate vivo, then it might possible functions by construction novel possess within one molecule multiple copies crucial hinge-CH2 associated structures. Although our previous work suggested hIgG4 was ineffective at ADCC, found so only individuals. In others, IgG4, indeed all subclasses able mediate ADCC. Overall, though, hIgG1 remains best choice isotype lytic therapy

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