POLYMERS IN DRUG-DELIVERY - IMMUNOTARGETING OF CARRIER-SUPPORTED CISPLATINUM COMPLEXES

Cisplatin (CDDP), a most powerful anticancer agent, was complexed to a polycarboxylic carrier carboxymethyldextran to form a platinum(II) mu lticomplex. Complexing occurs by displacement of the chlorine atoms of the platinum coordination complex by hydrogen of polymer side-chains to form mono- or bifunctional anchoring to adjacent carboxyls on the c arrier. The carrier-complexed drug interacted with DNA and was pharmac ologically active against tumor cells. The drug-carrier complex was im munotargeted to human epidermoid carcinoma (KB) tumors, using the mono clonal antibody (mAb) 108 directed against the epidermal growth factor receptor that is overexpressed on KB cells. Biotinyl-monoclonal antib ody was bound to a platinum(II)-carboxymethyldextran-avidin conjugate and the immune complex was administered into established subcutaneous KB tumors to evaluate its effects upon intratumor treatment. The resul ts showed that the immune complex was specifically effective in inhibi ting tumor growth. The antibody in the complex must be tumor-specific to anchor the drug-carrier multicomplex to the tumor site since an unb iotinylated antibody, or replacing the anti-KB antibody by a biotinyla ted antibody of a different specificity, resulted in reduced or abolis hed inhibitory effects.