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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing
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Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing

机译：克隆的转基因农场动物产生双特异性抗体，可杀死T细胞介导的肿瘤细胞

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摘要

Complex recombinant antibody fragments for modulation of immune function such as tumor cell destruction have emerged at a rapid pace and diverse anticancer strategies are being developed to benefit patients. Despite improvements in molecule design and expression systems, the quantity and stability, e.g., of single-chain antibodies produced in cell culture, is often insufficient for treatment of human disease, and the costs of scale-up, labor, and fermentation facilities are prohibitive. The ability to yield mg/ml levels of recombinant antibodies and the scale-up flexibility make transgenic production in plants and livestock an attractive alternative to mammalian cell culture as a source of large quantities of biotherapeutics. Here, we report on the efficient production of a bispecific single-chain antibody in the serum of transgenic rabbits and a herd of nine cloned, transgenic cattle. The bispecific protein, designated r28M, is directed to a melanoma-associated proteoglycan and the human CD28 molecule on T cells. Purified from the serum of transgenic animals, the protein is stable and fully active in mediating target cell-restricted T cell stimulation and tumor cell killing.
机译：用于调节免疫功能（例如肿瘤细胞破坏）的复杂重组抗体片段已经迅速出现，并且正在开发各种抗癌策略以使患者受益。尽管改进了分子设计和表达系统，但细胞培养中产生的单链抗体的数量和稳定性（例如，单链抗体）通常不足以治疗人类疾病，并且规模扩大，劳动力和发酵设施的成本高昂。产生毫克/毫升水平的重组抗体的能力和扩大的灵活性，使动植物中的转基因生产成为哺乳动物细胞培养的诱人替代品，因为它是大量生物治疗剂的来源。在这里，我们报告了在转基因兔和一群9个克隆的转基因牛的血清中有效产生双特异性单链抗体的情况。双特异性蛋白，称为r28M，针对T细胞上的黑色素瘤相关蛋白聚糖和人CD28分子。该蛋白是从转基因动物的血清中纯化得到的，在介导靶细胞限制性T细胞刺激和肿瘤细胞杀伤过程中是稳定且完全有效的。

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