期刊
CANCER IMMUNOLOGY RESEARCH
卷 7, 期 8, 页码 1244-1257出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-19-0036
关键词
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资金
- Cancer Prevention and Research Institute of Texas [RP140402, DP150056, RP180435, RP150551]
- Welch Foundation [AU-0042-20030616, I-1834]
- National Cancer Institute [1R01CA172268]
Therapeutic strategies are urgently needed for patients with acute myeloid leukemia (AML). Leukocyte immunoglobulinlike 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 immunocom-petent 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) antibodydependent cellular phagocytosis. Therefore, targeting LILRB4 with antibody represents an effective therapeutic strategy for treating monocytic AML.
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