Building Superior Biomolecules: Enhancing ADCs, Replacing ELISA, and Resurrecting ADEPT

Antibodies are important biological scaffolds used in biotherapeutics and diagnostics. The utility of antibodies can be expanded by coupling them with small-molecule drugs or proteins. Using both protein engineering and bioconjugation chemistry, we have created a series of highly-characterized antibody-conjugates that simultaneously deliver multiple drugs to induce new forms of synthetic lethality. Using these platforms, we are able to significantly increase the amount of drug that reaches a therapeutic target and demonstrate the applicability against HER2 positive cancers, as well as, drug-resistant bacteria. In separate approaches, we are utilizing split-enzyme technology to construct a new class of antibody-mediated diagnostics. These ‘wash-free’ homogenous immunoassays are as sensitive and more rapid than current technologies, without cumbersome processing steps. We have successfully constructed assays to measure protein biomarkers to follow cancer treatment and assays to monitor therapeutic drug levels. We are currently applying our platform to investigate important protein-protein interactions.