Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice.
Antibodies fused to human enzymes offer an alternative to specifically targeting tumors with antibodies linked to plant or bacterial toxins. Since large amounts of these reagents can be administered without eliciting non-specific toxicities, efficient methods of production are needed. The goal of this work was to express a complex immunoenzyme fusion protein (immunotoxin) in the mammary gland of transgenic mice. A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang). It was expressed in the mammary gland of mice and secreted into mouse milk. Expression levels in milk were approximately 0.8 g/l. The chimeric protein retained antibody binding activity and protein synthesis inhibitory activity equivalent to that of free Ang. It was specifically cytotoxic to human tumor cells in vitro.
Newton
D L
DL
Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
Pollock
D
D
DiTullio
P
P
Echelard
Y
Y
Harvey
M
M
Wilburn
B
B
Williams
J
J
Hoogenboom
H R
HR
Raus
J C
JC
Meade
H M
HM
Rybak
S M
SM
D000818:Animals; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011990:Receptors, Transferrin / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; C046366:angiogenin; D012259:Ribonuclease, Pancreatic