MODULATION OF DRUG-INDUCED CYTOTOXICITY BY A BISPECIFIC MONOCLONAL-ANTIBODY THAT RECOGNIZES THE EPIDERMAL GROWTH-FACTOR RECEPTOR AND DOXORUBICIN

A hybrid hybridoma secreting a bispecific hybrid mAb (bsmAb), which re cognizes both the epidermal growth factor receptor (EGF-R) and the dru g doxorubicin, was produced by somatic hybridization of two hybridomas . The bsmAb obtained was able to retarget doxorubicin cytotoxicity in vitro specifically on EGF-R-positive cells exerting at the same time a n antidotal effect on cells that did not overexpress the EGF-R. Distri bution studies in mice indicate that the bsmAb selectively delivers th e drug to tumour cells and modifies doxorubicin biodistribution with a statistically significant decrease of drug concentration in the intes tine, which is the main target of early anthracycline toxicity. In kee ping with this finding is the remarkable antidotal activity exerted by bsmAb in mice treated with doxorubicin, which is proved by retardatio n in loss of body weight and mortality. The effectiveness on tumour gr owth of the mAb followed by the administration of doxorubicin appears to be equal to that of the drug alone; however, the bsmAb exerts a rem arkable antidotal activity.