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Mining Naive Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility

机译:采矿幼稚兔抗体通过噬菌体展示进行治疗效用的单克隆抗体曲线

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摘要

Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large nave rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/ human Fab format and validated it by next -generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1 -and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor -engineered T cells, further corroborating the value of the na ve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs. (C) 2017 Elsevier Ltd. All rights reserved.
机译:由于它们的高亲和力和特异性,兔单克隆抗体(MAB)主要作为基础研究和诊断试剂证明了价值和潜力,但在某些情况下也是治疗剂。 为了加速访问兔MAB绕过免疫,我们产生由噬菌体展示文库代表的大型兔抗体曲目,其包括在嵌合兔/人Fab格式中的噬菌体展示文库中所代表的> 100亿独立抗体,并通过下一结论测序验证。 从该文库中选择的兔MAb的面板,针对两个新出现的癌症靶,ROR1和ROR2,揭示了高多样性,亲和力和特异性。 此外,ROR1-和ROR2靶向兔MAb证明了作为嵌合抗原受体 - 衰老T细胞的组分的治疗效用,进一步证实了Na Ve兔抗体文库的价值作为兔mAb的富含且几乎无限的兔来源。 (c)2017 Elsevier Ltd.保留所有权利。

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