| Structural highlights
Function
[LIRB4_HUMAN] Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Involved in the down-regulation of the immune response and the development of tolerance, e.g. towards transplants. Interferes with TNFRSF5-signaling and NF-kappa-B up-regulation. Inhibits receptor-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions.[1] [2]
Publication Abstract from PubMed
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.
Disrupting LILRB4/APOE Interaction by an Efficacious Humanized Antibody Reverses T-cell Suppression and Blocks AML Development.,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 XC, Xia N, Gao GF, Zhang N, Zhang CC, An Z Cancer Immunol Res. 2019 Jun 18. pii: 2326-6066.CIR-19-0036. doi:, 10.1158/2326-6066.CIR-19-0036. PMID:31213474[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chang CC, Ciubotariu R, Manavalan JS, Yuan J, Colovai AI, Piazza F, Lederman S, Colonna M, Cortesini R, Dalla-Favera R, Suciu-Foca N. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol. 2002 Mar;3(3):237-43. Epub 2002 Jan 28. PMID:11875462 doi:10.1038/ni760
- ↑ Cella M, Dohring C, Samaridis J, Dessing M, Brockhaus M, Lanzavecchia A, Colonna M. A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing. J Exp Med. 1997 May 19;185(10):1743-51. PMID:9151699
- ↑ 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 XC, Xia N, Gao GF, Zhang N, Zhang CC, An Z. Disrupting LILRB4/APOE Interaction by an Efficacious Humanized Antibody Reverses T-cell Suppression and Blocks AML Development. Cancer Immunol Res. 2019 Jun 18. pii: 2326-6066.CIR-19-0036. doi:, 10.1158/2326-6066.CIR-19-0036. PMID:31213474 doi:http://dx.doi.org/10.1158/2326-6066.CIR-19-0036
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