4ZFO

J22.9-xi: chimeric mouse/human antibody against human BCMA (CD269)

Summary for 4ZFO

• Entry DOI: 10.2210/pdb4zfo/pdb
• Descriptor: Tumor necrosis factor receptor superfamily member 17, J22.9-xi Fab, Light Chain, J22.9-xi Fab, Heavy Chain, ... (7 entities in total)
• Functional Keywords: antibody fab-ligand complex anti-bcma anti-tumor, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Single-pass type III membrane protein: Q02223
• Total number of polymer chains: 6
• Total formula weight: 106712.63

Authors

Marino, S.F.,Daumke, O.,Olal, D. (deposition date: 2015-04-21, release date: 2015-05-20, Last modification date: 2024-11-20)

Primary citation

Oden, F.,Marino, S.F.,Brand, J.,Scheu, S.,Kriegel, C.,Olal, D.,Takvorian, A.,Westermann, J.,Yilmaz, B.,Hinz, M.,Daumke, O.,Hopken, U.E.,Muller, G.,Lipp, M.
Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma.
Mol Oncol, 9:1348-1358, 2015

PubMed 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.

PubMed: 25953704
DOI: 10.1016/j.molonc.2015.03.010

Experimental method

X-RAY DIFFRACTION (1.895 Å)