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PDBsum entry 4zfo
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Immune system
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PDB id
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4zfo
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Contents |
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36 a.a.
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214 a.a.
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216 a.a.
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35 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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J22.9-xi: chimeric mouse/human antibody against human bcma (cd269)
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Structure:
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Tumor necrosis factor receptor superfamily member 17. Chain: f, k. Fragment: extracellular (n-terminal) domain, unp residues 1-54. Synonym: b-cell maturation protein, bcma, cd269. Engineered: yes. J22.9-xi fab, light chain. Chain: l. Engineered: yes. Other_details: fab light chain fragment of anti-bcma antibody j22.9-
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: tnfrsf17, bcm, bcma. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta2. Mus musculus. House mouse.
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Resolution:
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1.90Å
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R-factor:
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0.178
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R-free:
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0.209
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Authors:
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S.F.Marino,O.Daumke,D.Olal
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Key ref:
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F.Oden
et al.
(2015).
Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma.
Mol Oncol,
9,
1348-1358.
PubMed id:
DOI:
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Date:
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21-Apr-15
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Release date:
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20-May-15
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PROCHECK
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Headers
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References
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Q02223
(TNR17_HUMAN) -
Tumor necrosis factor receptor superfamily member 17 from Homo sapiens
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Seq:
Struc:
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184 a.a.
36 a.a.
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No UniProt id for this chain
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DOI no:
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Mol Oncol
9:1348-1358
(2015)
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PubMed id:
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Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma.
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F.Oden,
S.F.Marino,
J.Brand,
S.Scheu,
C.Kriegel,
D.Olal,
A.Takvorian,
J.Westermann,
B.Yilmaz,
M.Hinz,
O.Daumke,
U.E.Höpken,
G.Müller,
M.Lipp.
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ABSTRACT
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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.
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Links
