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

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Abstract
We have conjugated a murine monoclonal antibody (B4G7) against the human epidermal growth factor (EGF) receptor to gelonin, a 60S ribosome inactivating protein, via N‐succinimidyl‐3‐(2‐pyridyldithio)propionate (SPDP) and 2‐iminothiolane. The B4G7‐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 (Swiss/3T3). 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 10−8 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.

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