JAA-F11

Abstract

JAA-F11 antibody (Ab) is a monoclonal Ab that is specific for the Thomsen–Friedenreich antigen, Galβ1-3GalNAcα (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. ¹²⁴Iodine 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.

Keywords::

• breast cancer
• carbohydrate antigens
• carcinomas
• imaging
• immunotherapy
• JAA-F11
• metastasis
• positron emission tomography
• prostate cancer
• radiolocalization
• TF-Ag
• Thomsen-Friedenreich antigen
• tumor antigens

Acknowledgements

Much appreciation goes to S Morey (University at Buffalo), J Heimburg (University at Buffalo, now at Emory University), J Yan (University at Buffalo, now at Princeton University), R Chaturvedi (University at Buffalo, now at Seattle Biomedical Research Institute), V Glinskii (University of Missouri, Harry S Truman Memorial Veterans Hospital), M Sajjad (University at Buffalo) and D Hicks (Roswell Park Cancer Institute), all of whose careful work obtained the JAA-F11 data discussed. Special thanks to V Glinskii for composing Figure 1 and M Sajjad and R Chaturvedi for the images in Figure 2. The glycan-array analysis was conducted by the Protein–Carbohydrate Interaction Core H of The Consortium for Functional Glycomics funded by the National Institute of General Medical Sciences grant GM62116. The authors also thank R Alvarez (Director), R Cummings (Coordinator) and A Lee for assistance with the glycan array analysis. This work was supported by NIH R15AI49210-01, Peptide Mimics for Anti-Carbohydrate Response, UB STOR Product Development Fund, Congressionally Directed Medical Research Program W81XWH-04-1-0342 Grant ‘Immunization Using a Peptide Mimic of a Carbohydrate Tumor Antigen’, and Mark Diamond Grants for students J Heimburg, R Chaturvedi and J Yan.