6HXW

structure of human CD73 in complex with antibody IPH53

6HXW の概要

• エントリーDOI: 10.2210/pdb6hxw/pdb
• 分子名称: 5'-nucleotidase, IPH53 heavy chain, IPH53 light chain, ... (6 entities in total)
• 機能のキーワード: inhibitor antibody, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 214366.93

構造登録者

Roussel, A.,Amigues, B. (登録日: 2018-10-18, 公開日: 2019-08-28, 最終更新日: 2024-10-09)

主引用文献

Perrot, I.,Michaud, H.A.,Giraudon-Paoli, M.,Augier, S.,Docquier, A.,Gros, L.,Courtois, R.,Dejou, C.,Jecko, D.,Becquart, O.,Rispaud-Blanc, H.,Gauthier, L.,Rossi, B.,Chanteux, S.,Gourdin, N.,Amigues, B.,Roussel, A.,Bensussan, A.,Eliaou, J.F.,Bastid, J.,Romagne, F.,Morel, Y.,Narni-Mancinelli, E.,Vivier, E.,Paturel, C.,Bonnefoy, N.
Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies.
Cell Rep, 27:2411-2425.e9, 2019

PubMed Abstract: Immune checkpoint inhibitors have revolutionized cancer treatment. However, many cancers are resistant to ICIs, and the targeting of additional inhibitory signals is crucial for limiting tumor evasion. The production of adenosine via the sequential activity of CD39 and CD73 ectoenzymes participates to the generation of an immunosuppressive tumor microenvironment. In order to disrupt the adenosine pathway, we generated two antibodies, IPH5201 and IPH5301, targeting human membrane-associated and soluble forms of CD39 and CD73, respectively, and efficiently blocking the hydrolysis of immunogenic ATP into immunosuppressive adenosine. These antibodies promoted antitumor immunity by stimulating dendritic cells and macrophages and by restoring the activation of T cells isolated from cancer patients. In a human CD39 knockin mouse preclinical model, IPH5201 increased the anti-tumor activity of the ATP-inducing chemotherapeutic drug oxaliplatin. These results support the use of anti-CD39 and anti-CD73 monoclonal antibodies and their combination with immune checkpoint inhibitors and chemotherapies in cancer.

PubMed: 31116985
DOI: 10.1016/j.celrep.2019.04.091

実験手法

X-RAY DIFFRACTION (2.78 Å)