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Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma.

Abstract
Multiple myeloma (MM) is an aggressive incurable plasma cell malignancy with a median life expectancy of less than seven years. Antibody-based therapies have demonstrated substantial clinical benefit for patients with hematological malignancies, particular in B cell Non-Hodgkin's lymphoma. The lack of immunotherapies specifically targeting MM cells led us to develop a human-mouse chimeric antibody directed against the B cell maturation antigen (BCMA), which is almost exclusively expressed on plasma cells and multiple myeloma cells. The high affinity antibody blocks the binding of the native ligands APRIL and BAFF to BCMA. This finding is rationalized by the high resolution crystal structure of the Fab fragment in complex with the extracellular domain of BCMA. Most importantly, the antibody effectively depletes MM cells in vitro and in vivo and substantially prolongs tumor-free survival under therapeutic conditions in a xenograft mouse model. A BCMA-antibody-based therapy is therefore a promising option for the effective treatment of multiple myeloma and autoimmune diseases.
AuthorsFelix Oden, Stephen F Marino, Janko Brand, Susanne Scheu, Cathleen Kriegel, Daniel Olal, Anna Takvorian, Jörg Westermann, Buket Yilmaz, Michael Hinz, Oliver Daumke, Uta E Höpken, Gerd Müller, Martin Lipp
JournalMolecular oncology (Mol Oncol) Vol. 9 Issue 7 Pg. 1348-58 (Aug 2015) ISSN: 1878-0261 [Electronic] United States
PMID25953704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Chemical References
  • B-Cell Maturation Antigen
  • Epitopes
  • NF-kappa B
  • Tnfrsf17 protein, mouse
Topics
  • Animals
  • Antibody Affinity
  • B-Cell Maturation Antigen (immunology)
  • Disease Models, Animal
  • Epitopes (immunology)
  • Female
  • Glycosylation
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Multiple Myeloma (immunology)
  • NF-kappa B (metabolism)

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