Production of human monoclonal antibody in eggs of chimeric chickens
Production of human monoclonal antibody in eggs of chimeric chickens
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DOI：
10.1038/nbt1132
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发表时间：
2005-09-01
影响因子：
46.9
通讯作者：
Etches, RJ
中科院分区：
文献类型：
--
作者：
Zhu, L;van de Lavoir, MC;Etches, RJ
鸡输卵管的管状腺是蛋白质表达的一个有吸引力的系统，因为大量蛋白质沉积在鸡蛋中，鸡蛋的生产很容易扩大规模，并且已经建立了鸡蛋治疗的良好生产实践。在这里，我们检查了卵清蛋白（一种专门在鸡蛋清中大量产生的蛋白质）的上游和下游 DNA 序列驱动鸡蛋中人单克隆抗体组织特异性表达的能力。为了适应这些大的调控区域，我们建立并转染了鸡胚胎干 (cES) 细胞系，并形成了表达来自 cES 细胞衍生的管状腺细胞的 mAb 的嵌合体。来自高级嵌合体的卵含有高达 3 mg 的 mAb，该 mAb 具有增强的抗体依赖性细胞毒性 (ADCC)、非抗原糖基化、可接受的半衰期、出色的抗原识别和良好的内化率。
The tubular gland of the chicken oviduct is an attractive system for protein expression as large quantities of proteins are deposited in the egg, the production of eggs is easily scalable and good manufacturing practices for therapeutics from eggs have been established. Here we examined the ability of upstream and downstream DNA sequences of ovalbumin, a protein produced exclusively in very high quantities in chicken egg white, to drive tissue-specific expression of human mAb in chicken eggs. To accommodate these large regulatory regions, we established and transfected lines of chicken embryonic stem (cES) cells and formed chimeras that express mAb from cES cell-derived tubular gland cells. Eggs from high-grade chimeras contained up to 3 mg of mAb that possesses enhanced antibody-dependent cellular cytotoxicity (ADCC), nonantigenic glycosylation, acceptable half-life, excellent antigen recognition and good rates of internalization.