Antibody Directed Enzyme Prodrug Therapy (ADEPT)

Gene and Oncogene Targeting Team

Section: Section of Cancer Therapeutics (including the Cancer Research UK Centre for Cancer Therapeutics)

ADEPT is a two-step treatment for cancer. In the first step, an antibody–enzyme conjugate is administered. The antibody is raised against tumour specific antigens and localises to the tumour, carrying with it an exogenous enzyme. This is followed by administration of a prodrug, which is activated by the exogenous enzyme at the tumour site. We have previously used the chemically conjugated antibody fragment of a5b7 conjugated to CPG2 to activate the prodrugs CJS8 and CJS149 (ZD2767P) in clinical trials. We are now using a single chain antibody (scFv) fragment of an antibody raised against carcinoembryonic antigen (CEA), which is expressed in all colorectal tumours, fused to CPG2. This fusion protein localises to colorectal xenografts in vivo where it has been shown to activate the prodrug CJS149 (ZD2767P) to a potent cytotoxic agent. An ADEPT clinical trial in which we are measuring the prodrug pharmacokinetics from patients at the Royal Free Hospital is continuing.