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Figure S1 from Disrupting LILRB4/APOE Interaction by an Efficacious Humanized Antibody Reverses T-cell Suppression and Blocks AML Development

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posted on 2023-04-04, 01:03 authored by Xun Gui, Mi Deng, Hao Song, Yuanzhi Chen, Jingjing Xie, Zunling Li, Licai He, Fangfang Huang, Yixiang Xu, Yasuaki Anami, Hai Yu, Chenyi Yu, Leike Li, Zihao Yuan, Xiaoying Xu, Qihui Wang, Yan Chai, Tao Huang, Yi Shi, Kyoji Tsuchikama, X. Charlene Liao, Ningshao Xia, George F. Gao, Ningyan Zhang, Cheng Cheng Zhang, Zhiqiang An

Screening of anti-LILRB4 rabbit mAbs.

Funding

Cancer Prevention and Research Institute of Texa

Welch Foundation

National Cancer Institute

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ARTICLE 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.

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    Cancer Immunology Research

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    Keywords

    Hematological CancersLeukemiasImmunologyImmunomodulationImmunotherapyAntibody immunotherapy

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