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  • 标题:Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing
  • 本地全文:下载
  • 作者:Ludger Grosse-Hovest ; Sigrid Müller ; Rosa Minoia
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2004
  • 卷号:101
  • 期号:18
  • 页码:6858-6863
  • DOI:10.1073/pnas.0308487101
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 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.
  • 关键词:scFV ; nuclear transfer ; DNA microinjection ; antimelanoma ; anti-CD28
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