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

Item Type:Article
Title:Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma
Creators Name:Oden, F. and Marino, S.F. and Brand, J. and Scheu, S. and Kriegel, C. and Olal, D. and Takvorian, A. and Westermann, J. and Yilmaz, B. and Hinz, M. and Daumke, O. and Höpken, U.E. and Müller, G. and Lipp, M.
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.
Keywords:B Cell Maturation Antigen (BCMA), Immunotherapy, Multiple Myeloma, Monoclonal Antibody, Xenograft Mouse Model, High Resolution X-Ray Structure, Animals, Mice
Source:Molecular Oncology
Page Range:1348-1358
Date:August 2015
Official Publication:https://doi.org/10.1016/j.molonc.2015.03.010
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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