Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice

Antibodies fused to human enzymes offer an alternative to specifically targ eting tumors with antibodies linked to plant or bacterial toxins. Since lar ge amounts of these reagents can be administered without eliciting non-spec ific toxicities, efficient methods of production are needed. The goal of th is work was to express a complex immunoenzyme fusion protein (immunotoxin) in the mammary gland of transgenic mice. A chimeric mouse/human antibody di rected against the human transferrin receptor (E6) was fused at its CH2 dom ain to the gene for a human angiogenic ribonuclease, angiogenin (Ang). It w as expressed in the mammary gland of mice and secreted into mouse milk. Exp ression levels in milk were approximately 0.8 g/l. The chimeric protein ret ained antibody binding activity and protein synthesis inhibitory activity e quivalent to that of free Ang. It was specifically cytotoxic to human tumor cells in vitro. (C) 1999 Elsevier Science B.V. All rights reserved.