Novel Therapeutic Target for the Treatment of Lupus
Final rept. 1 Jul 2012-30 Jun 2014
LANKENAU INST OF MEDICAL RESEARCH WYNNEWOOD PA
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Many therapeutic strategies for SLE focus on the central role that autoantibody-producing B cells play in the pathology of this disorder. One general immunotherapeutic theme employs monoclonal antibodies mAb to interfere with, andor deplete, B cells to ultimately reduce disease causing autoantibody levels. However, current strategies are inherently limited because they are not specific for the disease state. Thus, treatments that can specifically block autoantibody production without compromising B cell function are needed. In our application we presented preliminary evidence in an in vivo model of a related autoimmune disease rheumatoid arthritis that showed antibodies to RhoB, a small GTPase blocked autoantibody secretion without affecting the overall B cell repertoire. This data led us to propose the objective of this DOD-Discovery Award, to evaluate the ability of anti-RhoB antibodies to reduce levels of pathologic autoantibodies, ultimately attenuating the severity of symptoms in the MRL-lpr murine model of SLE. Our results demonstrate that dosing with an anti- RhoB mAb reduces serum anti-dsDNA titers in MRL-lpr mice. Interestingly, the two anti-RhoB Igs tested exhibited differing effects on renal disease pathology in the SLE model. One anti-RhoB antibody reduced renal inflammation while the other did not. We plan to seek new funding to extend these intriguing observations, and better understand the therapeutic potential of these novel anti-RhoB biologics.
- Anatomy and Physiology
- Medicine and Medical Research