Enzyme-Prodrug Systems: Carboxylesterase/CPT-11

The development of enzyme-prodrug approaches for targeted treatment of human tumors has gained momentum in the last decade, especially with the advent of antibodies, viral vectors, and nonviral delivery systems that might be suitable for use in vivo. However, relatively few novel enzyme-prodrug combinations have been developed for use with these vectors. Because tumors differ in their intrinsic sensitivity to specific classes of chemotherapeutic agents, it is unlikely that any single enzyme-prodrug combination will be effective for all types of cancer. The design of additional vectors, enzymes, and prodrugs needs to be pursued. This section discusses the use of carboxylesterases (CEs) to activate the prodrug CPT-11 irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin.