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A Leishmania display platform for expression of human antibodies and glycoproteins

用于表达人类抗体和糖蛋白的利什曼原虫展示平台

基本信息

批准号：
521175-2017
负责人：
Jardim, Armando
金额：
$ 1.82万
依托单位：
McGill University
依托单位国家：
加拿大
项目类别：
Engage Grants Program
财政年份：
2017
资助国家：
加拿大
起止时间：
2017-01-01 至 2018-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=639719
关键词：
Leishmania display platform expression human

项目摘要

Immunoprecise Antibodies (IPA) is a Victoria, BC based company with expertise in development andproduction of murine and rabbit monoclonal antibodies (mAbs). To expand its competitive foot print in theantibody and recombinant protein production sector, IPA is exploring new strategies that will provide a morerapid turn around in the production of high quality therapeutic or research antibodies. In the production ofpolyclonal or monoclonal antibodies, one of the most time consuming steps is the immunization and boostingof host animals; which typically requires 50-60 days. To minimize this lag time IPA is interested in developinga new antibody production platform that circumvents the immunization step and will produced full length IgGantibodies that have the correct glycosylation patterns. Implementing this strategy will involve the developmentof an novel bicistronic vectors that will be used to create a surface display IgG library in the protozoanorganism Leishmania. Clones expressing the an IgG antibody that recognizes an antigen of interest can easilybe isolated using a biopanning approach. A major advantage for using Leishmania is that this organism hasglycosylation patterns that closely resemble thos observed on human and rabbit IgG antibodies. This projectwill provide that proof of principle data require for the ultimate creation of a human IgG surface display library.

IPA是一家总部设在不列颠哥伦比亚省维多利亚市的公司，专门从事鼠和兔单抗(MAbs)的开发和生产。为了扩大其在抗体和重组蛋白生产领域的竞争足迹，IPA正在探索新的战略，这些战略将在高质量治疗或研究抗体的生产中迅速扭转局面。在多克隆或单克隆抗体的生产中，最耗时的步骤之一是宿主动物的免疫和加强；这通常需要50-60天。为了最大限度地减少这一滞后时间，IPA有兴趣开发一种新的抗体生产平台，该平台可以绕过免疫步骤，并将生产具有正确糖基化模式的全长IgG抗体。实施这一战略将涉及开发一种新型的双顺反子载体，该载体将用于在原生动物利什曼原虫中创建表面展示的免疫球蛋白G库。表达识别感兴趣抗原的免疫球蛋白抗体的克隆可以使用生物扫描方法很容易地分离出来。使用利什曼原虫的一个主要优点是，这种生物体的糖基化模式与人和兔的抗体上观察到的糖基化模式非常相似。该项目将提供最终创建人类免疫球蛋白表面展示文库所需原则数据证明。