Structural characterization of JAA-F11-Fab by X-ray crystallography

Abstract

Thomsen Friedenreich antigen (TF-Ag), is a carbohydrate antigen found on many types of tumors, including breast, prostate, bladder and ovarian. Passive transfer of JAA-F11, a monoclonal anti-TF-Ag antibody, has been shown to block metastasis and provide a survival advantage in mice with metastatic breast cancer. Some cancer patients have an immune response to TF-Ag and this correlates with a better prognosis. Creation of an immune response in the patient to TF-Ag has clinical potential, however, it is difficult to form this response because carbohydrate antigens form a less effective T-cell independent response whereas, peptide antigens evoke a more effective T-cell dependent immune response process, causing isotype switching, affinity maturation and memory development. Immunization with peptide mimics of TF-Ag created an immune response to TF-Ag. In order to improve the response, the spatial arrangement and intermolecular interactions of the peptides with JAA-F11 need to be studied by X-ray crystallography to produce the best peptide mimic. JAA-F11 has been purified, crystallized and the structure has been determined at a resolution of 2.1Å on which, molecular modelling with the peptides is underway to understand the binding in order to improve the peptides. This research has the potential to develop a novel vaccine against breast cancer.