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

Tech ID: 00-01

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 inflammatory 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-ĸB 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 - in vivo studies and ongoing work is assessing the potential to utilize the region of TALL-1 critical in the formation of virus like structure to enhance the potency of other TNF-family molecules.

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

Patent Status -U.S. Patent # 6,475,987 and 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 WO # 2003/35846.

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

Publication

• 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 .

For Further Information, Contact:
Emmanuel Hilaire, PhD
Licensing Associate
Intellectual Property and Technology Commercialization Program
National Jewish Health
1400 Jackson Street, Room M206a
Denver, CO 80206
Voice: (303) 398-1053
Fax: (303) 270-2352
hilairee@njc.org