Chemically Programmable CDK12 Degrader-ADCs for Solid Tumors

Cyclin-dependent kinase 12 (CDK12) is a key regulator of transcriptional programs that maintain genome stability and support the survival of multiple aggressive cancers, yet efforts to develop CDK12-targeted therapies have been limited by systemic toxicity. Dr. Zhou and her team seek to address this challenge by developing antibody-based delivery platforms carrying CDK12 small-molecule inhibitors and degraders to selectively deliver these agents to tumor cells. By integrating advances in protein engineering, antibody design, and payload innovation, they aim to establish strategies for improving the therapeutic index of kinase-targeted medicines. Using CDK12-targeted therapeutics as a model, this research will define general protein engineering principles that could expand the range of therapeutic payloads delivered through antibody-drug conjugates.