Shawn Owen, Christine Nervig, and Samuel Hatch Publication in ACS Medicinal Chemistry Letters
In a recent publication in ACS Medicinal Chemistry Letters entitled “Complementation Dependent Enzyme Prodrug Therapy Enables Targeted Activation of Prodrug on HER2-Positive Cancer Cells”, Professor Shawn Owen and students Christine Nervig and Samuel Hatch detail the development of a split enzyme therapeutic platform for the activation of cephem-based prodrugs at tumor sites. This strategy seeks to resurrect the concept of antibody-directed enzyme prodrug therapy (ADEPT) by unlocking enzyme activity only at the target site. Two antibody mimics, each armed with half of a split enzyme, bind to neighboring epitopes on HER2 which allows for proximity induced refolding of the active enzyme. Demonstrating its potential against a known clinical target, Owen and coworkers show that the split enzyme system can complement on cells and cleave prodrug, resulting in 7-fold higher toxicity of the activated prodrug over prodrug treatment alone and toxicity comparable to intact enzyme controls.
Congratulations to all three!
