title: Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing.
abstract: 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.
authors.affiliation: Institute for Cell Biology, Department of Immunology, Eberhard Karls University, 72076 Tübingen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Grosse-Hovest
authors.forename: Sigrid
authors.initials: S
authors.lastname: Müller
authors.forename: Rosa
authors.initials: R
authors.lastname: Minoia
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Valeri
authors.initials: V
authors.lastname: Zakhartchenko
authors.forename: Hendrik
authors.initials: H
authors.lastname: Wenigerkind
authors.forename: Caroline
authors.initials: C
authors.lastname: Lassnig
authors.forename: Urban
authors.initials: U
authors.lastname: Besenfelder
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
authors.forename: Simon D
authors.initials: SD
authors.lastname: Lytton
authors.forename: Gundram
authors.initials: G
authors.lastname: Jung
authors.forename: Gottfried
authors.initials: G
authors.lastname: Brem
mesh_terms: D000818:Animals; D002417:Cattle / Q000276:immunology*; D019976:Cloning, Organism; D006801:Humans; D019169:Jurkat Cells; D009369:Neoplasms / Q000276:immunology*; D011817:Rabbits / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*