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Anti-CD79 Antibody Offers Novel Approach to Therapy in Autoimmune Disease, Transplantation and Lymphoma

技術優勢

Treatment of autoimmune conditions such as rheumatoid arthritis, lupus, and diabetes.Treatment of B cell neoplasiasPrevention of tissue rejection

技術應用

Treatment of autoimmune conditions such as rheumatoid arthritis, lupus, and diabetes.Treatment of B cell neoplasiasPrevention of tissue rejection

詳細技術說明

B lymphocytes play fundamental roles in the pathogenesis of autoimmune disease as well as transplant rejection. Current technologies for treatment of many lymphomas, leukemias, transplant rejection and some autoimmune disorders include monoclonal antibodies (mAb) that target and deplete B cell populations. Recovery from these treatments requires an extended period of time during which patients are immunosuppressed and therefore susceptible to opportunistic infections. In addition, this modality does not eliminate all B lineage cells and thus may not be appropriate for all pathologic conditions involving B lymphocytes.Clusters of Differentiation 79 (CD79) is a transmembrane protein found exclusively in B cells that is the transducer component of B-cell receptor (BCR), generating a signal following recognition of antigen by the BCR. As a consequence CD79 is an ideal candidate molecule for B cell-targeted therapy.Investigators have shown that administration of an anti-mouse CD79 targeting BCR in a mouse model of lupus, decreased autoantibody production (suppressed B cell responses), decreased skin pathology, and increased survival from 20% to 80%. Furthermore they established that anti-CD79a/b antibodies (intact, or mutants incompetent to bind IgG receptors and activate the complement cascade) block the development of disease and ameliorate ongoing target organ injury in mouse models of Rheumatoid Arthritis and Type 1 Diabetes.In later experiments they developed a proprietary monoclonal antibody against human CD79 (Curly 14) that has the capacity to desensitize the BCR in vitro.Further experiments will involve the characterization of the effectiveness of Curly 14 for modulating immune disease, understanding Curly 14 binding affinity, determination of the antibody binding site and the ability to destabilize and/or desensitize B cells in huSCID and human CD79 knockin mouse models.

*Abstract

Dr. Cambier and his laboratory discovered that in certain circumstances, subunits of the B cell antigen receptor (BCR) become dissociated rendering the receptor incompetent to transduce activating signals. Based on these observations they produced antibodies against the BCR transducers, CD79a and b, and found that they ΓÇ£desensitizeΓÇØ the BCR and suppress the immune response, autoimmunity, and growth of non-HodgkinΓÇÖs B lymphoma. These anti-CD79 mAbs show therapeutic potential to induce reversible inhibition of BCR signaling and B cell function. This technology exploits the unique qualities of the BCR to reversibly suppress signaling for therapeutic use in autoimmunity, cancer and transplantation. Receptor desensitization and therapeutic efficacy has been demonstrated in vitro and in vivo.

*Principal Investigation

Name: John Cambier, Chairman

Department: Integrated Department of Immunology

主要類別

診斷/治療

細分類別

其他疾病

國家/地區

美國