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

Technology Benefits

Novel extracellular targets

Technology Application

Therapy for inflammatory and immune-related diseases.

Detailed Technology Description

National Jewish Health scientists have demonstrated the following:TALL-1 is expressed specifically in monocytes and macrophagesTALL-1 is down regulated by mytogensBCMA specifically binds to TALL-1 and activates NF-?B through a TRAF5/TRAF-6 pathwayThe 3D structure of the TALL-1 monomer by crystallography60 TALL-1 monomers can form a virus like structure in physiological conditionsThe TALL-1 region critical for the formation of this virus-like structure has been identifiedDeletion of such region disrupts the virus like assembly but does not affect the binding to BCMA and the NF-kappaB activationSeveral genes have been identified and shown to be induced by TALL-1 and NF-kappaB dependentFurther 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.

Supplementary Information

Inventor: Shu, Hong Bing
Priority Number: US6475987B1
IPC Current: C07K0014705 | C12N001512 | A61K003800
US Class: 5140189 | 514012 | 4350691 | 5140135 | 5140206 | 530350 | 5360235
Assignee Applicant: National Jewish Medical and Research Centernver
Title: Tall-1 receptor homologues
Usefulness: Tall-1 receptor homologues
Summary: For identifying compounds used to regulate B lymphocyte proliferation (claimed), associated with B-lymphocyte associated autoimmune diseases. Compounds which regulate the interaction between (I) and its receptor are used to regulate monocyte, macrophage and B lymphocyte mediated immune responses. (I) and the nucleic acid sequences encoding it, and amino acids specific for it can be used in diagnostic assays.
Novelty: Isolated TALL-1 protein is used to identify compounds that regulate B lymphocyte proliferation, used to treat B lymphocyte associated autoimmune disorders

Industry

Chemical/Material

Sub Category

Chemical/Material Application

*Abstract

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.

*Principal Investigator

Name: Gongyi Zhang, Professor

Department: Integrated Department of Immunology

Country/Region

USA