6K7O

Complex structure of LILRB4 and h128-3 antibody

6K7O の概要

• エントリーDOI: 10.2210/pdb6k7o/pdb
• 分子名称: Leukocyte immunoglobulin-like receptor subfamily B member 4, h128-3 Fab heavy chain, h128-3 Fab light chain (3 entities in total)
• 機能のキーワード: lilrb4, antibody, immune therapy., immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 235461.63

構造登録者

Song, H.,Chai, Y.,Xu, X.,Gao, F.G. (登録日: 2019-06-08, 公開日: 2019-07-03, 最終更新日: 2023-11-22)

主引用文献

Gui, X.,Deng, M.,Song, H.,Chen, Y.,Xie, J.,Li, Z.,He, L.,Huang, F.,Xu, Y.,Anami, Y.,Yu, H.,Yu, C.,Li, L.,Yuan, Z.,Xu, X.,Wang, Q.,Chai, Y.,Huang, T.,Shi, Y.,Tsuchikama, K.,Liao, X.C.,Xia, N.,Gao, G.F.,Zhang, N.,Zhang, C.C.,An, Z.
Disrupting LILRB4/APOE Interaction by an Efficacious Humanized Antibody Reverses T-cell Suppression and Blocks AML Development.
Cancer Immunol Res, 7:1244-1257, 2019

PubMed Abstract: Therapeutic strategies are urgently needed for patients with acute myeloid leukemia (AML). Leukocyte immunoglobulin-like receptor B4 (LILRB4), which suppresses T-cell activation and supports tissue infiltration of AML cells, represents an attractive drug target for anti-AML therapeutics. Here, we report the identification and development of an LILRB4-specific humanized mAb that blocks LILRB4 activation. This mAb, h128-3, showed potent activity in blocking the development of monocytic AML in various models including patient-derived xenograft mice and syngeneic immunocompetent AML mice. MAb h128-3 enhanced the anti-AML efficacy of chemotherapy treatment by stimulating mobilization of leukemia cells. Mechanistic studies revealed four concordant modes of action for the anti-AML activity of h128-3: (i) reversal of T-cell suppression, (ii) inhibition of monocytic AML cell tissue infiltration, (iii) antibody-dependent cellular cytotoxicity, and (iv) antibody-dependent cellular phagocytosis. Therefore, targeting LILRB4 with antibody represents an effective therapeutic strategy for treating monocytic AML.

PubMed: 31213474
DOI: 10.1158/2326-6066.CIR-19-0036

実験手法

X-RAY DIFFRACTION (3.004 Å)