Human Polyclonal Antibody Production in Chickens

性状（由申请方提供）： 免疫疗法是对抗人类疾病的强大武器，但 目前的技术仅限于从小鼠遗传上产生的单克隆抗体 工程化以表达人序列抗体库。一项重大进展 将是产生多克隆人类抗体， 在治疗应用中增加抗体性能的动物。的 鸡的生物学特性使其成为这种动物宿主的理想候选者。的 第一阶段的研究计划将测试人类免疫球蛋白基因是否可以 在鸡免疫的情况下进行适当的加工和表达， 系统在其种系构型中的人重链基因座将是 将其引入鸡胚胎干细胞和嵌合鸡中， 进行了将分析嵌合体的人重链产生 在他们的血清和B细胞中。在第二阶段，该方法将全面 通过构建含有灭活的 内源性免疫球蛋白基因和人重链基因的拷贝以及内源性免疫球蛋白基因之一， 用于产生全人抗体的轻链基因座。这项技术 将使得能够产生单克隆和多克隆人序列 比现在可能的更高亲和力和有效性的抗体。 拟定商业应用： 拟议的研究描述了在鸡中生产治疗性人多克隆抗体的技术。人类抗体治疗各种人类疾病的市场机会很大。与目前的抗体生产方法相比，拟议的技术将提供几个优势，因此将很容易占领这一市场的份额。

DESCRIPTION (provided by the applicant): Monoclonal antibodies for immunotherapy are a powerful weapon in the battle against human disease, but current technology is limited to monoclonals generated from mice genetically engineered to express a human sequence antibody repertoire. A major advance would be to generate polyclonal human antibodies in a phylogenetically distant animal for increased antibody performance in therapeutic applications. The biology of the chicken makes it an ideal candidate for such an animal host. The proposed research in Phase I will test whether human immunoglobulin genes can be properly processed and expressed in the context of the chicken immune system. The human heavy chain locus in its germline configuration will be introduced into chicken embryonic stem cells and chimeric chickens will be made. Chimeras will be analyzed for the production of a human heavy chain repertoire in their serum and B cells. In Phase II, the approach will be fully developed by constructing a strain of chickens containing inactivated endogenous immunoglobulin genes and copies of the human heavy and one of the light chain loci for the production of fully human antibodies. This technology will enable the production of both nomoclonal and polyclonal human sequence antibodies of higher avidity and effectiveness than now possible. PROPOSED COMMERCIAL APPLICATION: The proposed research describes technology to produce therapeutic human polyclonal antibodies in the chicken. There are large-market opportunities for human antibodies to treat a wide variety of human diseases. The proposed technology will offer several advantages over current antibody production methods and thus will easily capture a share of this market.