Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells.
We have conjugated the murine monoclonal antibody (528) against the human epidermal growth factor receptor (EGFR) to mammalian pancreatic ribonuclease (RNase) via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolene (2-IT). The conjugate showed dose-dependent cytotoxicity against EGFR-producing squamous cancer cells (A431, TE8, TE5, Ca9-22) and no detectable cytotoxicity against EGFR-deficient small-cell lung cancer cells (H69). The cytotoxicity of the conjugate was positively correlated with the EGFR numbers of each cell line. The addition of excess 528 antibody to the medium protected A431 cells from the conjugate cytotoxicity. This immunoconjugate might be useful for targeted treatment of squamous cell carcinomas hyperexpressing EGFR.
Suwa
T
T
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Ueda
M
M
Jinno
H
H
Ozawa
S
S
Kitagawa
Y
Y
Ando
N
N
Kitajima
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D004220:Disulfides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000201:enzymology; D012260:Ribonucleases / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004220:Disulfides; D018796:Immunoconjugates; D066246:ErbB Receptors; D012260:Ribonucleases