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Applications of phage-displayed antibody library for antibody discovery and engineering.

机译：噬菌体展示抗体库在抗体发现和工程设计中的应用。

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摘要

Antibodies are one of the most useful molecules with affinity of binding and specificity for in vitro and in vivo diagnosis, or for immunotherapy of human diseases. In recent years, phage-displayed antibody library has been widely adopted to select tailor-made antibodies in a fast, high-throughput mode, as an alternative of traditional hybridoma technology. Although phage display has been introduced for about 20 years, the applications and development of this technology still have a rich space to be explored.;Attempts are made in the present study to extend three applications of the phage displayed antibody library in antibody discovery and engineering. Firstly, a CDR3-randomized phage-displayed scFv library was constructed from genomic DNA of mouse. Following biopanning, anti-peptide of mas oncoprotein scFvs were isolated and identified. These results illustrate the potential use of the genomic phage-displayed library for anti-peptide antibodies selection. Secondly, we described the isolation of anti-idiotypic scFvs against a chimeric anti-CD22 mAb from an immunized phage-displayed scFv library. The isolated anti-Id scFvs were able to capture the immune response of chimeric anti-CD22 mAb with high specificity. This reagent will enhance our understanding of the therapeutic mechanism of anti-CD22 mAb in non-Hodgkin's lymphoma treatment, and may be applied to probe the pharmacokinetics, tissue distribution, and modulation of anti-CD22 mAb in vivo.;Our approach enables us to isolate selective and sensitive anti-idiotypic antibodies and could be exploited for other antibodies with clinical and biological applications. Thirdly, we profile a strategy to select and identify markers on tumor cell surface using phage-displayed antibodies from mice bearing xenograft tumor. Our data imply that passive antibodies in cancer patients may be obtained from the immune repertoire of cancer patients. Besides, we found a cell surface antigen was up-regulated more than 3-fold in mas-expressing cells. We further use the targeting antibody to construct a tumor endoprotease-activated immunotoxin.;In conclusion, we have attempted various approaches to identify specific anti-peptide scFvs, anti-idiotypic scFvs and passive anti-tumor scFvs. These results extend the applications of phage display technology in antibody discovery and engineering.
机译：抗体是具有结合亲和力和特异性的最有用的分子之一，用于体外和体内诊断或人类疾病的免疫治疗。近年来，作为传统杂交瘤技术的替代方法，已广泛采用噬菌体展示的抗体文库以快速，高通量的模式选择特制的抗体。尽管噬菌体展示已经被引入了约20年，但这项技术的应用和发展仍有广阔的探索空间。;本研究试图扩大噬菌体展示抗体库在抗体发现和工程中的三种应用。首先，从小鼠的基因组DNA构建了CDR3随机噬菌体展示的scFv文库。生物淘选后，分离并鉴定了mas癌蛋白scFv的抗肽。这些结果说明了将基因组噬菌体展示的文库用于抗肽抗体选择的潜在用途。其次，我们描述了从免疫噬菌体展示的scFv文库中分离出针对嵌合抗CD22 mAb的抗独特型scFv。分离的抗Id scFv能够以高特异性捕获嵌合抗CD22 mAb的免疫应答。该试剂将增强我们对非霍奇金淋巴瘤治疗中抗CD22 mAb的治疗机制的了解，并可用于探测体内抗CD22 mAb的药代动力学，组织分布和调节。分离选择性和敏感的抗独特型抗体，可以用于其他具有临床和生物学应用的抗体。第三，我们概述了使用携带异种移植肿瘤的小鼠的噬菌体展示抗体选择和鉴定肿瘤细胞表面标记的策略。我们的数据表明，癌症患者中的被动抗体可以从癌症患者的免疫库中获得。此外，我们发现细胞表面抗原在表达mas的细胞中被上调了3倍以上。我们进一步使用靶向抗体来构建肿瘤内切蛋白酶激活的免疫毒素。总之，我们已经尝试了多种方法来鉴定特异性的抗肽scFv，抗独特型scFv和被动性抗肿瘤scFv。这些结果扩展了噬菌体展示技术在抗体发现和工程中的应用。

著录项

  • 作者

    Zhao, Qi.;

  • 作者单位

    The Chinese University of Hong Kong (Hong Kong).;

  • 授予单位 The Chinese University of Hong Kong (Hong Kong).;
  • 学科 Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 250 p.
  • 总页数 250
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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