Structural investigation of a bispecific antibody for treatment of HER2-expressing cancers
Zanidatamab is an antibody being evaluated in clinical trials to treat breast cancer, biliary tract cancer and gastroesophageal adenocarcinomas linked to the overabundance of a protein known as HER2. Zanidatamab was developed to bind to two copies of HER2 in tandem instead of one, increasing its binding affinity and improving its inhibition of HER2 tumor-promoting activities. The binding of each zanidatamab to two copies of HER2 is proposed to form a network of HER2 linked by zanidatamab. Our project aims to use cryogenic electron microscopy to determine the structure of the HER2-zanidatamab complex. In addition to providing molecular details of the complex, our study will provide a framework for structurally characterizing related antibodies and guide future development of biological therapeutics.