Julio A. Camarero, Ph.D.

University of Southern California, Los Angeles, CA

2016 B-Cells, New treatments

Could refocusing a current, ineffective lupus treatment (BAFF) create a new and improved therapy?

The study and what it means to patients

“Our innovative research aims to improve on the current treatment which uses antibodies to eliminate the molecule known as BAFF that stimulates the production of B-cells. We will target specific receptors, molecules that respond to and activate the BAFF molecule, rather than BAFF itself, to increase effectiveness and provide a new and exciting treatment for lupus.”


Despite compelling evidence that the molecule BAFF, which stands for B-cell activating factor, plays a significant role in the development of lupus, current treatment that targets this molecule offers only a modest, if any, clinical benefit to patients. Our research will study the therapeutic effect of targeting a specific set of BAFF receptors that seems to be the main culprit in causing damage. Selectively inhibition of two of the BAFF receptors could offer a novel and superior treatment for lupus.

Technical Summary

The loss of B cell tolerance to self-antigens can lead to the production of pathogenic autoantibodies that characterize autoimmune diseases, such as systemic lupus erythematosus (SLE). In healthy individuals, competition for a limited supply of the survival factor BAFF plays a key role in the elimination of autoreactive B cells. In SLE patients, BAFF levels are elevated, which lead to increased numbers of peripheral self-reactive B cells, heightened B cell activation, and autoantibody production. Despite compelling evidence for a substantial contributory role for BAFF to SLE pathogenesis, belimumab, a human IgG1? mAb that binds and neutralizes soluble BAFF, offers only a modest clinical benefit at best. Understanding how excess BAFF promotes SLE pathology is complicated by the fact that three distinct receptors bind BAFF: BR3 (also called BAFF-R), BCMA, and TACI. BR3 mediates survival and maturation of immature B cells, whereas BCMA promotes plasma cell survival. TACI is essential for central B cell tolerance and acts as a negative regulator of the B cell compartment. Here we propose to develop selective antagonists directed against the BR3 receptor and the BCMA receptor. By eliminating BAFF signaling coupled to the survival of B cells (BR3-mediated) and plasma cells (BCMA-mediated) while sparing TACI signaling necessary for central B cell tolerance, we will selectively inhibit the disease-promoting aspects of BAFF signaling.