Structure of Cancer Antigen Mesothelin and Its Complex with Therapeutic Antibodies

Mesothelin is a differentiation antigen expressed at high levels on the surface of many cancers; its interaction with cancer antigen CA-125 can lead to metastasis. Mesothelin has been the subject of intensive investigations as a potential cancer antigen for immunotherapy. Structures of a fragment of mesothelin, full-length mesothelin alone and in complex with the Fab fragment of the therapeutic antibody MORAb-009, as well as a complex of its C-terminal fragment containing the majority of the identified shedding sites, or the shedding-resistant fragment, with monoclonal antibody 15B6 were obtained. The glycosylation profile of mesothelin purified from A431/H9 cells and patient ascites were obtained by glycoproteomics