Jaa-f11: extending the life of mice with breast cancer

Abstract

JAA-F11 antibody (Ab) is a monoclonal Ab that is specific for the Thomsen-Friedenreich antigen, Galbeta1-3GalNAcalpha (TF-Ag). TF-Ag, discovered in the late 1920s, is a tumor-associated carbohydrate Ag of many clinically widespread carcinomas. In a mouse model, JAA-F11 Ab significantly extended median survival time of animals with metastatic 4T1 breast tumors and caused > 50% inhibition of lung metastasis. (124)Iodine labeled JAA-F11 Ab in in vivo micro positron emission tomography showed tumor specificity in a mouse breast tumor model, with no preferential uptake by any other organ. Human cancer cell adhesion to vascular endothelium was also blocked by JAA-F11. Structural specificity of the Ab was shown with glycan array analysis and indicated that this Ab, unlike many other Abs to TF-Ag, will not bind to a related glycolipid on natural killer cells, kidney or spleen. Patients with higher levels of naturally occurring anti-TF-Ag Ab appear to have a better prognosis, indicating that passive transfer of JAA-F11 or active immunization, resulting in production of anti-TF-Ag Ab, would clinically be beneficial for the patient.