Antibody-enzyme fusion proteins for cancer therapy

Abstract

Advances in biomolecular technology have allowed the development of genetically fused antibody-enzymes. Antibody-enzyme fusion proteins have been used to target tumors for cancer therapy in two ways. In one system, an antibody-enzyme is pretargeted to the tumor followed by administration of an inactive prodrug that is converted to its active form by the pretargeted enzyme. This system has been described as antibody-directed enzyme prodrug therapy. The other system uses antibody-enzyme fusion proteins as direct therapeutics, where the enzyme is toxic in its own right. The key feature in this approach is that the antibody is used to internalize the toxic enzyme into the tumor cell, which activates cell-death processes. This antibody-enzyme system has been largely applied to deliver ribonucleases. This article addresses these two antibody-enzyme targeting strategies for cancer therapy from concept to (pre)clinical trials.