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AB0023 In Vivo Effects of Epratuzumab, A Monoclonal Antibody Targeting Human CD22, on B Cell Function in Human CD22 Knock-In (HUKI) Mice
  1. C. Brandl1,
  2. L. Özgör1,
  3. M. Wöhner1,2,
  4. A. Shock3,
  5. L. Nitschke1
  1. 1University of Erlangen, Erlangen, Germany
  2. 2Research Institute of Molecular Pathology (IMP), Vienna, Austria
  3. 3UCB Pharma, Slough, United Kingdom

Abstract

Background Epratuzumab is a humanized monoclonal antibody that targets the B cell-specific protein CD22 and is currently in Phase 3 clinical trials in patients (pts) with systemic lupus erythematosus (SLE). Epratuzumab does not deplete B cells and appears to act in an immunomodulatory fashion, eg. by inhibiting activation through the B cell receptor (BCR).1 It has also been shown to modulate adhesion molecule expression on B cells and their responsiveness to chemokines.2

Objectives The present study aimed to understand the effect of epratuzumab on B cells in vivo using human CD22 knock-in (Huki) mice, in which the B cells express the human CD22 gene instead of the murine gene.3

Methods Huki mice received a single intravenous injection (0.5mg) of epratuzumab and, at various time points up to Week (Wk) 12, B cell sub-populations in blood, spleen, bone marrow and lymph nodes were measured, along with B cell activation and homing markers. Ex vivo functional assays were also performed: Ca+ flux, apoptosis and CD22 internalization on B cells were measured by flow cytometry and the proliferation of B cells was assessed after in vivo administration of BrdU.

Results Epratuzumab-treated mice showed rapid and long-lasting human CD22 internalization on B cells from all organs up to Wk8 and an increase of B cell apoptosis (an increase of cells in sub G1 phase) ex vivo. Furthermore, decreased BCR-activated Ca+-flux was demonstrated after epratuzumab treatment in vitro. However, BrdU incorporation in several B cell subsets was unchanged at early time points and there were no consistent effects demonstrated on the numbers or proportions of such subsets in various organs at any time point up to Wk12.

Conclusions Epratuzumab treatment of Huki mice induces functional effects on B cells assessed ex vivo but does not seem to strongly influence B cell development and B cell populations in various organs. These data have implications for understanding the effects of epratuzumab treatment on B cell function in SLE pts.

References

  1. Sieger N. Arth Rheum 2013;65:770.

  2. Daridon C. Arth Res Ther 2010;12:R204.

  3. Wöhner M. Eur J Immunol 2012;42:3009.

Acknowledgements C. Brandl and L. Özgör contributed equally to the work.

The authors acknowledge Costello Medical Consulting for editorial assistance which was funded by UCB Pharma.

Disclosure of Interest C. Brandl Grant/research support: UCB Pharma, L. Özgör Grant/research support: UCB Pharma, M. Wöhner: None declared, A. Shock Employee of: UCB Pharma, L. Nitschke Grant/research support: UCB Pharma

DOI 10.1136/annrheumdis-2014-eular.1751

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