6K7O

Complex structure of LILRB4 and h128-3 antibody

Summary for 6K7O

• Entry DOI: 10.2210/pdb6k7o/pdb
• Descriptor: Leukocyte immunoglobulin-like receptor subfamily B member 4, h128-3 Fab heavy chain, h128-3 Fab light chain (3 entities in total)
• Functional Keywords: lilrb4, antibody, immune therapy., immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 235461.63

Authors

Song, H.,Chai, Y.,Xu, X.,Gao, F.G. (deposition date: 2019-06-08, release date: 2019-07-03, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.004 Å)