EVade™ demonstrate selectivity for cancer cells on their own, however their efficacy can be enhanced by conjugation of the RNase to a tumor-targeting molecule. Tumor targeting strategies employ antibodies, peptides, or small molecules that bind specifically to receptors on cancer cells.
A subset of the EVade™ RNases has been produced with one or more sites that can be used for conjugation. A one to one EVade™ RNase to folate conjugate was produced by conjugation of folate to a region of the ribonuclease that caused evasion of ribonuclease inhibitor. The EVade™ RNase:folate conjugate was 25-fold more toxic to a folate overexpressing cancer cell line (JAR cells) than a non-targeted EVade™ RNase. Based on results in other systems, targeting the EVade™ RNases could result in a two to three order of magnitude increase in cytotoxicity.
Quintessence Biosciences is currently looking for partners with targeting or delivery methods to further enable this application.