Novel Therapeutic Target for the Treatment of Lupus

Abstract

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, and/or 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 purpose of this study, 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. We have not yet completed testing the anti-RhoB therapy in the SLE model and subsequently received approval of an extension without funds for the award period. Thus far, our data suggests that dosing with the anti-RhoB antibodies produces a trend towards a decrease in autoantibody titers and proteinuria; however, we are currently performing another treatment experiment that we hope will enable us to achieve statistical significance and have a better understanding of the effects resulting from targeting RhoB.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2013
Accession Number
ADA600721

Entities

People

  • Lisa D Laury-Kleintop

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Antibodies
  • Arthritis
  • Autoimmune Diseases
  • Biomedical Research
  • Department Of Defense
  • Disease Attributes
  • Diseases And Disorders
  • Electronic Mail
  • Immune System Diseases
  • Lupus
  • Pathology
  • Production
  • Proteins
  • Secretion
  • Tissues
  • United States

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology
  • Molecular and Cellular Biology
  • Neurological Diseases/Conditions/Disorders