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Type of publication: Journal Article
Type of document: Full Paper

Year: 2004

Authors: Grosse-Hovest, L; Müller, S; Minoia, R; Wolf, E; Zakhartchenko, V; Wenigerkind, H; Lassnig, C; Besenfelder, U; Müller, M; Lytton, SD; Jung, G; Brem, G

Title: Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing.

Source: Proc Natl Acad Sci U S A. 2004; 101(18):6858-6863

Authors Vetmeduni Vienna:

Besenfelder Urban
Brem Gottfried
Müller Mathias
Müller Simone

Vetmed Research Units
Institute of Animal Breeding and Genetics

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.

Keywords Pubmed: Animals
Cloning, Organism
Jurkat Cells

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