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  • Shawn Owen, Christine Nervig, and Samuel Hatch Publication in ACS Medicinal Chemistry Letters

Shawn Owen, Christine Nervig, and Samuel Hatch Publication in ACS Medicinal Chemistry Letters

Dec 13, 2022

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!

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