[Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing] -- Agrobiogen
>>Published online before print April 22, 2004
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0308487101
Applied Biological Sciences
Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing
( scFV | nuclear transfer | DNA microinjection | antimelanoma | anti-CD28 )
Ludger Grosse-Hovest *, Sigrid Müller , Rosa Minoia , Eckhard Wolf ¶, Valeri Zakhartchenko ¶, Hendrik Wenigerkind ¶, Caroline Lassnig ||**, Urban Besenfelder **, Mathias Müller ||**, Simon D. Lytton , Gundram Jung *, and Gottfried Brem ||
*Institute for Cell Biology, Department of Immunology, Eberhard Karls University, 72076 Tübingen, Germany; Agrobiogen, Thalmannsdorf 25, 86567 Hilgertshausen, Germany; ¶Institute of Molecular Animal Breeding, Ludwig Maximilians University, 81377 Munich, Germany; ||Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria; **Department of Biotechnology in Animal Production, Institute for Agrobiotechnology, Konrad Lorenz Strasse 20, A-3430 Tulln, Austria; and Department of Animal Production, University of Bari, 70122 Bari, Italy
Edited by Ellen S. Vitetta, University of Texas Southwestern Medical Center, Dallas, TX, and approved March 18, 2004 (received for review December 19, 2003)
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.<<
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