4ZFO

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

4ZFO の概要

• エントリーDOI: 10.2210/pdb4zfo/pdb
• 分子名称: Tumor necrosis factor receptor superfamily member 17, J22.9-xi Fab, Light Chain, J22.9-xi Fab, Heavy Chain, ... (7 entities in total)
• 機能のキーワード: antibody fab-ligand complex anti-bcma anti-tumor, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type III membrane protein: Q02223
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 106712.63

構造登録者

Marino, S.F.,Daumke, O.,Olal, D. (登録日: 2015-04-21, 公開日: 2015-05-20, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.895 Å)