Augmentation of Cytotoxic Drug Action by Antibodies Directed at Cell Surface

Abstract

THE concept of attaching cytotoxic agents to tumour-specific antibodies in the treatment of cancer is therapeutically attractive. In this way the specificity of the agents would be increased and their systemic toxicity reduced. This immunochemotherapeutic approach has been successfully applied in experimental systems when the cytotoxic agent has been covalently bound to the antibody^1–3. Similar success has been reported with the nitrogen mustard chlorambucil, merely physically adsorbed on to the globulin fraction from tumour-specific antiserum without the actual formation of a covalent bond⁴. It is surprising that antibody could act as a carrier for chlorambucil under these conditions, as has been proposed⁵, as the two molecules would be expected to dissociate in the in vivo environment. It is, therefore, probable that the increased cytotoxicity of chlorambucil in the presence of antibody is attributable to some other mechanism. The experiments described here are an attempt to elucidate this problem further.