[Frontiers in Bioscience S4, 840-863, January 1, 2012]

Anti-Thomsen-Friedenreich-Ag (anti-TF-Ag) potential for cancer therapy

Adel Almogren1,2, Julia Abdullah3, Kshipra Ghapure2, Kimiko Ferguson2, Vladislav V. Glinsky4,5, Kate Rittenhouse-Olson2,3,6,1

1Department Of Pathology, College of Medicine King Saud University, Riyadh, 11461 Saudi Arabia, 2Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, Buffalo, NY 14214, USA 3Department of Microbiology, and Immunology, University at Buffalo, Buffalo, NY 14214, USA, 4Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, 65212, 5Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201, 6Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Synthesis and accumulation
4. Lectins
4.1. Proliferation stimulating lectins
4.1.1. Mechanism of cell proliferation
4.1.2. Peanut agglutinin
4.1.3. Amaranthus caudatus lectin (ACL or ACA)
4.2. Proliferation inhibiting lectins
4.2.1. Mechanism of cell proliferation inhibition
4.2.2. Jacalin
4.2.3. Agaricus bisporus lectin
4.2.4. Sclerotium rolfsii lectin
4.2.5. Agrocybe aegerita lectin
4.2.6. Beauveria bassiana lectin
4.2.7. Xeocomus chrysenteron lectin
5. Monoclonal antibodies
6. Human antibodies
6.1. Human anti-TF-Ag antibodies
6.2. Human anti-TF-Ag antibodies and the relation to tumor prognosis
7. Role in metastasis
8. Vaccines
9. Acknowledgement
10. References

1. ABSTRACT

Thomsen-Friedenreich antigen (TF-Ag) is the disaccharide (Gal beta1-3 GalNAc alpha), which is also known as the core 1 structure. The presence of this disaccharide on the surface of ~90% of carcinomas is due to altered glycosylation in these tumors. TF-Ag plays a role in the adhesive properties of tumor cells involved in metastasis. Treatment of mice with JAA-F11, a monoclonal antibody to TF-Ag alpha inhibited lung metastasis and improved prognosis in a mouse breast cancer model. The presence of naturally occurring antibodies to TF-Ag in cancer patients is related to improved prognosis. The pancarcinoma expression of TF-Ag, combined with the evidence of a mechanistic role for TF-Ag in cancer spread, show that this target would have clinical utility. The presence of naturally occurring antibody to TF-Ag indicates that increasing the anti-TF-Ag antibody would be safe for the cancer patient and indicates that tolerance would not have to be broken to create this immune response. Finally, the prognostic improvements seen clinically and in animal models indicate that this is an important vaccine target.