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Friederich Miescher Institute [W. W., I-M. H., B. G., N. E. H.], and Research Department, Pharmaceuticals Division, Ciba-Geigy, Ltd. [M. M.], CH-4002 Basel, Switzerland
A high percentage of human breast and ovarian tumors display amplified c-erbB-2 gene copies, leading to overexpression of the growth factor receptor. Its membrane location and elevated expression make the erbB-2 protein an appropriate target for a directed tumor therapy. We have used recombinant DNA technology to produce a single-chain antibody-exotoxin A (scFv-ETA) fusion protein which specifically binds the human erbB-2 receptor. The scFv portion is composed of the heavy- and light-chain variable domains of a monoclonal antibody which recognizes the extracellular domain of the human erbB-2 receptor. The bacterially produced scFv-ETA protein was shown to bind specifically to cells expressing the human erbB-2 protein. The scFv-ETA inhibits protein synthesis in erbB-2-expressing tumor cells at doses ranging from 2 to 200 ng/ml and is cytotoxic for these cells at equivalent doses. In athymic nude mice, administration of the scFv-ETA inhibited the growth of erbB-2-overexpressing human ovarian carcinoma cells.
1 To whom requests for reprints should be addressed, at Friedrich Miescher Institute, P. O. Box 2543, CH-4002 Basel, Switzerland.
Received 6/10/92. Accepted 9/ 9/92.
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