Selective killing of squamous carcinoma cells by an immunotoxin that recognizes the egf receptor

✍ Scribed by Soji Ozawa; Masakazu Ueda; Nobutoshi Ando; Osahiko Abe; Shinsei Minoshima; Nobuyoshi Shimizu

• Book ID: 102867418
• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: French
• Weight: 663 KB
• Volume: 43
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910430128

✦ Synopsis

We have conjugated a murine monoclonal antibody (8447) against the human epidermal growth factor (EGF) receptor to gelonin, a 60s ribosome inactivating protein, via N-succinimi-dyI-3-(2-pyridyldithio)propionate (SPDP) and 2-iminothiolane. The 64G7-gelonin conjugate bound to the cell surface in proportion to the number of EGF receptors and competed with B4G7 antibody for binding to EGF receptors. The conjugate killed EGF receptor-hyperproducing squamous carcinoma cells (A431, NA, Ca9-22, TE5). and to some extent, human fibroblasts (HFO). It did not kill EGF receptor-deficient small-cell lung cancer cells (H69) and mouse fibroblasts (Swissl313). Free B4G7, gelonin or a mixture of B4G7 and gelonin did not kill A431 cells. The number of EGF receptors was correlated to cytotoxicity at lo-* M of the conjugate, and the data were fitted to the regression equation: y = -35.83 log x +233.4

(correlation coefficient = -0.9995). These results suggest that the B4G7-gelonin conjugate may be a useful weapon for targeting therapy to squamous-cell carcinomas.