Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing.
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.
Grosse-Hovest
Ludger
L
Institute for Cell Biology, Department of Immunology, Eberhard Karls University, 72076 Tübingen, Germany.
Müller
Sigrid
S
Minoia
Rosa
R
Wolf
Eckhard
E
Zakhartchenko
Valeri
V
Wenigerkind
Hendrik
H
Lassnig
Caroline
C
Besenfelder
Urban
U
Müller
Mathias
M
Lytton
Simon D
SD
Jung
Gundram
G
Brem
Gottfried
G
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*