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Targeted Oncology

, Volume 13, Issue 1, pp 39–47 | Cite as

The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in, Multiple Myeloma

  • Eric Sanchez
  • Emily J. Smith
  • Moryel A. Yashar
  • Saurabh Patil
  • Mingjie Li
  • Autumn L. Porter
  • Edward J. Tanenbaum
  • Remy E. Schlossberg
  • Camilia M. Soof
  • Tara Hekmati
  • George Tang
  • Cathy S. Wang
  • Haiming Chen
  • James R. BerensonEmail author
Review Article

Abstract

B-cell maturation antigen (BCMA) was originally identified as a cell membrane receptor, expressed exclusively on late stage B-cells and plasma cells (PCs). Investigations of BCMA as a target for therapeutic intervention in multiple myeloma (MM) were initiated in 2007, using cSG1 as a naked antibody (Ab) as well as an Ab–drug conjugate (ADC) targeting BCMA, ultimately leading to ongoing clinical studies for previously treated MM patients. Since then, multiple companies have developed anti-BCMA-directed ADCs. Additionally, there are now three bispecific antibodies in development, which bind to both BCMA and CD3ε on T-cells. This latter binding results in T-cell recruitment and activation, causing target cell lysis. More recently, T-cells have been genetically engineered to recognize BCMA-expressing cells and, in 2013, the first report of anti-BCMA-chimeric antigen receptor T-cells showed that these killed MM cell lines and human MM xenografts in mice. BCMA is also solubilized in the blood (soluble BCMA [sBCMA]) and MM patients with progressive disease have significantly higher sBCMA levels than those responding to treatment. sBCMA circulating in the blood may limit the efficacy of these anti-BCMA-directed therapies. When sBCMA binds to B-cell activating factor (BAFF), BAFF is unable to perform its major biological function of inducing B-cell proliferation and differentiation into Ab-secreting PC. However, the use of γ-secretase inhibitors, which prevent shedding of BCMA from PCs, may improve the efficacy of these BCMA-directed therapies.

Notes

Acknowledgements

We would like to thank Jenna Riehl for her assistance in the submission of the manuscript.

Compliance with Ethical Standards

Funding

None.

Conflict of Interest

Eric Sanchez, Mingjie Li, Cathy S. Wang, Haiming Chen, and James R. Berenson hold ownership interest (including patents) in OncoTracker, Inc. Emily J. Smith, Moryel Yashar, Saurabh Patil, Autumn L. Porter, Edward J. Tanenbaum, Remy E. Schlossberg, Camilia M. Soof, and George Tang declare that they have no conflict of interest.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Eric Sanchez
    • 1
  • Emily J. Smith
    • 1
  • Moryel A. Yashar
    • 1
  • Saurabh Patil
    • 1
  • Mingjie Li
    • 1
  • Autumn L. Porter
    • 1
  • Edward J. Tanenbaum
    • 1
  • Remy E. Schlossberg
    • 1
  • Camilia M. Soof
    • 1
  • Tara Hekmati
    • 1
  • George Tang
    • 1
  • Cathy S. Wang
    • 1
  • Haiming Chen
    • 1
  • James R. Berenson
    • 1
    Email author
  1. 1.Institute for Myeloma & Bone Cancer ResearchWest HollywoodUSA

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