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 e pidermal growth factor receptor (EGFR) to mammalian pancreatic ribonuclease (RNase) via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-imi nothiolene (2-IT). The conjugate showed dose-dependent cytoxicity against E GFR-producing squamous cancer cells (A431, TE8, TE5, Ca9-22) and no detecta ble cytoxicity against EGFR-deficient small-cell lung cancer cells (H69). T he cytotoxicity of the conjugate was positively correlated with the EGFR nu mbers of each cell line. The addition of excess 528 antibody to the medium protected A431 cells from the conjugate cytotoxicity. This immuno-conjugate might be useful for targeted treatment of squamous cell carcinomas hyperex pressing EGFR.