TALL-1 and its Receptor BCMA: Molecular Targets for the Development of Therapies Against Autoimmune Diseases

Tech ID: 02-01

Summary - Researchers at National Jewish Health have discovered that TALL-1, a member of the tumor necrosis factor (TNF), plays an important role in the modulation of immune responses by costimulating B lymphocyte proliferation. TALL-1 has been crystallized and its 3D structure resolved. In addition, the investigators have isolated a receptor at the surface of B lymphocytes, B cell maturation protein (BCMA), that specifically binds to TALL-1. Various TALL- induced genes have also been identified. Therefore, BCMA, the 3D structure of TALL-1and TALL-1-induced genes can constitute several target routes for the development of treatments against autoimmune diseases.

Potential Applications - Therapy for inflammatory and immune-related diseases.

Advantages of Invention - Novel extracellular targets

State of Development - National Jewish Health scientists have demonstrated the following:

• TALL-1 is expressed specifically in monocytes and macrophages
• TALL-1 is down regulated by mytogens
• BCMA specifically binds to TALL-1 and activates NF-?B through a TRAF5/TRAF-6 pathway
• The 3D structure of the TALL-1 monomer by crystallography
• 60 TALL-1 monomers can form a virus like structure in physiological conditions
• The TALL-1 region critical for the formation of this virus-like structure has been identified
• Deletion of such region disrupts the virus like assembly but does not affect the binding to BCMA and the NF-kappaB activation
• Several genes have been identified and shown to be induced by TALL-1 and NF-kappaB dependent

Further R&D Required - The investigators have created a Fc-BCMA mutant that has increased avidity and specificity to B lymphocytes. This is currently being tested in mice models of autoimmune diseases.

Publications

• Shu et al. (1999) J. Leukoc. Biol. 65(5): 680-683
• Shu and Johnson (2000) Proc. Natl. Acad. Sci.97(16): 9156-9161
• Liu et al. (2002) Cell. 108: 383-394
• Xu et al. (2002) J. Leukoc. Biol. 72(2): 410-416
• Liu et al. (2003) Nature. 423: 49-56

Patent Status - U.S. Patents #6,475,987, #7,825,089 and #7,994,115, other U.S. and foreign patents pending covering TALL-1 and its 3D structure, BCMA and homologues, and methods of use. Published U.S. Patent Application #20070015695 and published International Patent Application #WO2003/35846.

Inventors - Hong-Bing Shu, PhD, Gongyi Zhang, PhD

Licensing Potential - Available for licensing in some fields of use.

For Further Information, Contact:
Emmanuel Hilaire, PhD
Manager
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206
Voice: 303.398.1262
Fax: 303.270.2352
HilaireE@njhealth.org