Antibody prodrugs for cancer.

: The toxicity of potent new biological therapies for cancer has limited their utility. By improving tumor specificity, antibody prodrugs can widen or even create a therapeutic window for anticancer agents that are difficult or impossible to use otherwise because of poor tolerability.: This review will describe the current status of the field of antibody prodrugs, focusing on Probody therapeutics, including the principles behind their design, application to a variety of different antibody-based therapies, preclinical examples of their activity and safety, and early results of Phase 1 trials.: Proof of concept for the antibody prodrug approach, which is defined as demonstration of potent antitumor activity with improved safety, has been extensively established preclinically as well as preliminarily in early clinical trials in human patients. However, experience with antibody prodrugs is limited, and important challenges remain. Principal among them are how to design the molecules to provide the most effective protection from toxicities while preserving efficacy, how to optimize clinical pharmacology, and how to determine which among the many possible clinical applications is the best use of this promising technology.