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 deveioped to benefit patients. Despite improvements in molecule design and expression systems, the quantity and stabiiity, e.g., of singie-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 yieid mg/ml levels of recombinant antibodies and the scale-up fiexibility make transgenic production in plants and iivestock 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 singie-chain antibody in the serum of transgenic rabbits arid a herd of nine cioned, transgenic cattie. The bispecific protein, designated r28M, Is directed to a meianoma-associated proteoglycan and the human CD28 molecule on T cells. Purified from the serum of transgenic animais, the protein is stable and fully active in mediating target cell-restricted T cell stimulation and tumor cell killing. scFv nuclear transfer DNA microinjection I antimelanoma anti-CD28