Functions and therapeutic targets of Siglec-mediated infections, inflammations and cancers

Crocker, 2007, Siglecs and their roles in the immune system, Nat Rev Immunol, 7, 255, 10.1038/nri2056 von Gunten, 2008, Basic and clinical immunology of siglecs, Ann N Y Acad Sci, 1143, 61, 10.1196/annals.1443.011 Chang, 2014, The interplay between Siglecs and sialylated pathogens, Glycobiology, 24, 818, 10.1093/glycob/cwu067 O'Neill, 2013, Sialoadhesin—a macrophage-restricted marker of immunoregulation and inflammation, Immunology, 138, 198, 10.1111/imm.12042 Salminen, 2009, Siglec receptors and hiding plaques in Alzheimer's disease, J Mol Med (Berl), 87, 697, 10.1007/s00109-009-0472-1 Raj, 2014, CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer's disease susceptibility, Hum Mol Genet, 23, 2729, 10.1093/hmg/ddt666 Bornhöfft, 2018, Siglecs: a journey through the evolution of sialic acid-binding immunoglobulin-type lectins, Dev Comp Immunol, 86, 219, 10.1016/j.dci.2018.05.008 Varki, 2001, Loss of N-glycolylneuraminic acid in humans: mechanisms, consequences, and implications for hominid evolution, Am J Phys Anthropol, Suppl 33, 54, 10.1002/ajpa.10018 Varki, 2010, Uniquely human evolution of sialic acid genetics and biology, Proc Natl Acad Sci USA, 107, 8939, 10.1073/pnas.0914634107 Crocker, 2008, Siglecs as positive and negative regulators of the immune system, Biochem Soc Trans, 36, 1467, 10.1042/BST0361467 Blasius, 2006, Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12, Blood, 107, 2474, 10.1182/blood-2005-09-3746 Takamiya, 2013, The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway, Glycobiology, 23, 178, 10.1093/glycob/cws139 Angata, 2014, Associations of genetic polymorphisms of Siglecs with human diseases, Glycobiology, 24, 785, 10.1093/glycob/cwu043 Walter, 2008, ITIM-dependent endocytosis of CD33-related Siglecs: role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2, J Leukoc Biol, 83, 200, 10.1189/jlb.0607388 Jellusova, 2012, Regulation of B cell functions by the sialic acid-binding receptors siglec-G and CD22, Front Immunol, 2, 96, 10.3389/fimmu.2011.00096 Simmons, 1988, Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells, J Immunol, 141, 2797, 10.4049/jimmunol.141.8.2797 Falco, 1999, Identification and molecular cloning of p75/AIRM1, a novel member of the sialoadhesin family that functions as an inhibitory receptor in human natural killer cells, J Exp Med, 190, 793, 10.1084/jem.190.6.793 Nicoll, 1999, Identification and characterization of a novel siglec, siglec-7, expressed by human natural killer cells and monocytes, J Biol Chem, 274, 34089, 10.1074/jbc.274.48.34089 von Gunten, 2005, Siglec-9 transduces apoptotic and nonapoptotic death signals into neutrophils depending on the proinflammatory cytokine environment, Blood, 106, 1423, 10.1182/blood-2004-10-4112 Crocker, 2001, Siglecs in the immune system, Immunology, 103, 137, 10.1046/j.0019-2805.2001.01241.x Angata, 2006, Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates, FASEB J, 20, 1964, 10.1096/fj.06-5800com Angata, 2007, Siglec-15: an immune system Siglec conserved throughout vertebrate evolution, Glycobiology, 17, 838, 10.1093/glycob/cwm049 Yamaji, 2005, Characterization of inhibitory signaling motifs of the natural killer cell receptor Siglec-7: attenuated recruitment of phosphatases by the receptor is attributed to two amino acids in the motifs, Glycobiology, 15, 667, 10.1093/glycob/cwi048 Angata, 2018, Possible influences of endogenous and exogenous ligands on the evolution of human Siglecs, Front Immunol, 9, 2885, 10.3389/fimmu.2018.02885 Dankwa, 2016, Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite, Nat Commun, 7, 11187, 10.1038/ncomms11187 Rumer, 2012, Siglec-6 is expressed in gestational trophoblastic disease and affects proliferation, apoptosis and invasion, Endocr Relat Cancer, 19, 827, 10.1530/ERC-11-0379 Chen, 2009, CD24 and Siglec-10 selectively repress tissue damage-induced immune responses, Science, 323, 1722, 10.1126/science.1168988 Sammar, 2017, Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface, Histochem Cell Biol, 147, 565, 10.1007/s00418-016-1531-7 Wang, 2011, Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology, Glycobiology, 21, 1038, 10.1093/glycob/cwr039 Wang, 2012, Evolution of siglec-11 and siglec-16 genes in hominins, Mol Biol Evol, 29, 2073, 10.1093/molbev/mss077 Wang, 2012, Specific inactivation of two immunomodulatory SIGLEC genes during human evolution, Proc Natl Acad Sci USA, 109, 9935, 10.1073/pnas.1119459109 Orr, 2007, CD33 responses are blocked by SOCS3 through accelerated proteasomal-mediated turnover, Blood, 109, 1061, 10.1182/blood-2006-05-023556 Lübbers, 2018, Modulation of immune tolerance via Siglec-sialic acid interactions, Front Immunol, 9, 2807, 10.3389/fimmu.2018.02807 Mehta, 2010, Myelin-associated glycoprotein (MAG) protects neurons from acute toxicity using ganglioside-dependent mechanism, ACS Chem Neurosci, 1, 215, 10.1021/cn900029p Varchetta, 2012, Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes, PLoS One, 7, 10.1371/journal.pone.0045821 Cao, 2008, SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non-functional alleles in humans, Eur J Immunol, 38, 2303, 10.1002/eji.200738078 Hitomi, 2007, Association of CD22 gene polymorphism with susceptibility to limited cutaneous systemic sclerosis, Tissue Antigens, 69, 242, 10.1111/j.1399-0039.2007.00801.x Jitoku, 2011, Association study of Nogo-related genes with schizophrenia in a Japanese case-control sample, Am J Med Genet B Neuropsychiatr Genet, 156B, 581, 10.1002/ajmg.b.31199 Gao, 2010, Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma, Eur J Hum Genet, 18, 713, 10.1038/ejhg.2009.239 Ishii, 2017, Influence of SIGLEC9 polymorphisms on COPD phenotypes including exacerbation frequency, Respirology, 22, 684, 10.1111/resp.12952 Ali, 2014, Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus, J Exp Med, 211, 1231, 10.1084/jem.20131853 Angata, 2014, Association of serum interleukin-27 with the exacerbation of chronic obstructive pulmonary disease, Physiol Rep, 2, 10.14814/phy2.12069 Lee, 2010, Hypermucoviscosity associated with Klebsiella pneumoniae-mediated invasive syndrome: a prospective cross-sectional study in Taiwan, Int J Infect Dis, 14, e688, 10.1016/j.ijid.2010.01.007 Lee, 2014, Aspirin enhances opsonophagocytosis and is associated to a lower risk for Klebsiella pneumoniae invasive syndrome, BMC Infect Dis, 14, 47, 10.1186/1471-2334-14-47 Lee, 2014, Sialic acid involved in hypermucoviscosity phenotype of Klebsiella pneumoniae and associated with resistance to neutrophil phagocytosis, Virulence, 5, 673, 10.4161/viru.32076 Chang, 2014, Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B Streptococcus, J Mol Med, 92, 951, 10.1007/s00109-014-1157-y Liu, 2017, Sialic acids in the immune response during sepsis, Front Immunol, 8, 1601, 10.3389/fimmu.2017.01601 Jones, 2003, Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake, Mol Microbiol, 49, 1213, 10.1046/j.1365-2958.2003.03634.x Heikema, 2013, Siglec-7 specifically recognizes Campylobacter jejuni strains associated with oculomotor weakness in Guillain-Barré syndrome and Miller Fisher syndrome, Clin Microbiol Infect, 19, E106, 10.1111/1469-0691.12073 Heikema, 2010, Characterization of the specific interaction between sialoadhesin and sialylated Campylobacter jejuni lipooligosaccharides, Infect Immun, 78, 3237, 10.1128/IAI.01273-09 Schwarz, 2017, Paired Siglec receptors generate opposite inflammatory responses to a human-specific pathogen, EMBO J, 36, 751, 10.15252/embj.201695581 Roy, 2016, Leishmania donovani utilize sialic acids for binding and phagocytosis in the macrophages through selective utilization of Siglecs and impair the innate immune arm, PLoS Negl Trop Dis, 10, 10.1371/journal.pntd.0004904 Erdmann, 2009, Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E), Cell Microbiol, 11, 1600, 10.1111/j.1462-5822.2009.01350.x Jacobs, 2010, Molecular interaction of Siglecs (sialic acid-binding Ig-like lectins) with sialylated ligands on Trypanosoma cruzi, Eur J Cell Biol, 89, 113, 10.1016/j.ejcb.2009.10.006 Orlandi, 1992, A malaria invasion receptor, the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum recognizes the terminal Neu5Ac(alpha 2-3)Gal− sequences of glycophorin A, J Cell Biol, 116, 901, 10.1083/jcb.116.4.901 Air, 2014, Influenza virus-glycan interactions, Curr Opin Virol, 7, 128, 10.1016/j.coviro.2014.06.004 Ito, 1998, Molecular basis for the generation in pigs of influenza A viruses with pandemic potential, J Virol, 72, 7367, 10.1128/JVI.72.9.7367-7373.1998 Nguyen, 2006, Loss of Siglec expression on T lymphocytes during human evolution, Proc Natl Acad Sci USA, 103, 7765, 10.1073/pnas.0510484103 Jobe, 2016, Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region, J Leukoc Biol, 99, 1089, 10.1189/jlb.2A0815-361R Brunetta, 2009, The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer–cell subsets associated with high levels of HIV-1 viremia, Blood, 114, 3822, 10.1182/blood-2009-06-226332 Suenaga, 2010, Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses, Proc Natl Acad Sci USA, 107, 866, 10.1073/pnas.0913351107 Suenaga, 2015, Sialic acids on Varicella-Zoster virus glycoprotein B are required for cell-cell Fusion, J Biol Chem, 290, 19833, 10.1074/jbc.M114.635508 Puttur, 2013, Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance, PLoS Pathog, 9, 10.1371/journal.ppat.1003648 Yokoi, 2008, Inhibition of FceRI-dependent mediator release and calcium flux from human mast cells by Siglec-8 engagement, J Allergy Clin Immunol, 121, 499, 10.1016/j.jaci.2007.10.004 Ando, 2008, Siglec-9 enhances IL-10 production in macrophages via tyrosine-based motifs, Biochem Biophys Res Commun, 369, 878, 10.1016/j.bbrc.2008.02.111 Chen, 2014, Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1, Elife, 3, 10.7554/eLife.04066 Bochner, 2009, Siglec-8 on human eosinophils and mast cells, and Siglec-F on murine eosinophils, are functionally related inhibitory receptors, Clin Exp Allergy, 39, 317, 10.1111/j.1365-2222.2008.03173.x Jang, 2014, Additive anti-allergic effects of anti-interleukin-33 and anti-Siglec-F treatments in a murine model of allergic asthma, Cent Eur J Immunol, 39, 426, 10.5114/ceji.2014.47724 Mizrahi, 2014, Siglec-7 is an inhibitory receptor on human mast cells and basophils, J Allergy Clin Immunol, 134, 230, 10.1016/j.jaci.2014.03.031 Mahajan, 2016, Sialic acids and autoimmune disease, Immunol Rev, 269, 145, 10.1111/imr.12344 Xiong, 2014, Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis, Rheumatology (Oxford), 53, 250, 10.1093/rheumatology/ket342 York, 2007, A macrophage marker, siglec-1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type I interferons and toll-like receptor agonists, Arthritis Rheum, 56, 1010, 10.1002/art.22382 Wilhelm, 2016, Siglec-1-positive plasmacytoid dendritic cells (pDCs) in human peripheral blood: a semi-mature and myeloid-like subset imbalanced during protective and autoimmune responses, Clin Immunol, 163, 42, 10.1016/j.clim.2015.12.001 Madge, 2016, Structural characterisation of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt's lymphoma (BL) Daudi cells by NMR spectroscopy, Sci Rep, 6, 36012, 10.1038/srep36012 Müller, 2014, The role of CD22 and Siglec-G in B-cell tolerance and autoimmune disease, Nat Rev Rheumatol, 10, 422, 10.1038/nrrheum.2014.54 Müller, 2015, Siglec-G deficiency leads to autoimmunity in aging C57BL/6 mice, J Immunol, 195, 51, 10.4049/jimmunol.1403139 Litschke, 2014, CD22 and Siglec-G regulate inhibition of B-cell signaling by sialic acid ligand binding and control B-cell tolerance, Glycobiology, 24, 807, 10.1093/glycob/cwu066 Karasawa, 2015, Vascular-resident CD169-positive monocytes and macrophages control neutrophil accumulation in the kidney with ischemia-reperfusion injury, J Am Soc Nephrol, 26, 896, 10.1681/ASN.2014020195 Pepin, 2015, Soluble Siglec-5 associates to PSGL-1 and displays anti-inflammatory activity, J Am Soc Nephrol, 26, 896 Fong, 2015, Immunomodulatory activity of extracellular Hsp70 mediated via paired receptors Siglec-5 and Siglec-14, EMBO J, 34, 2775, 10.15252/embj.201591407 Nguyen, 2014, Role of Siglec-7 in apoptosis in human platelets, PLoS One, 9, 10.1371/journal.pone.0106239 McMillan, 2014, Siglec-E promotes β2-integrin-dependent NADPH oxidase activation to suppress neutrophil recruitment to the lung, J Biol Chem, 289, 20370, 10.1074/jbc.M114.574624 Rashmi, 2009, Siglec-9 and SHP-1 are differentially expressed in neonatal and adult neutrophils, Pediatr Res, 66, 266, 10.1203/PDR.0b013e3181b1bc19 Jia, 2015, Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells, J Allergy Clin Immunol, 135, 799, 10.1016/j.jaci.2015.01.004 Banda, 2012, Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid, J Biol Chem, 287, 28852, 10.1074/jbc.M112.364182 Taylor, 2010, Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid, J Exp Med, 207, 1637, 10.1084/jem.20100575 Samraj, 2015, A red meat-derived glycan promotes inflammation and cancer progression, Proc Natl Acad Sci USA, 112, 542, 10.1073/pnas.1417508112 Schwarz, 2015, Siglec receptors impact mammalian lifespan by modulating oxidative stress, eLife, 7, 4 Fehervari, 2015, A Siglec link to aging, Nat Immunol, 16, 598 Groh, 2016, Sialoadhesin promotes neuroinflammation-related disease progression in two mouse models of CLN disease, Glia, 64, 792, 10.1002/glia.22962 Walker, 2015, Association of CD33 polymorphism rs3865444 with Alzheimer's disease pathology and CD33 expression in human cerebral cortex, Neurobiol Aging, 36, 571, 10.1016/j.neurobiolaging.2014.09.023 Schwarz, 2016, Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline, Proc Natl Acad Sci USA, 113, 74, 10.1073/pnas.1517951112 DeBellard, 1996, Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via interaction with a sialoglycoprotein, Mol Cell Neurosci, 7, 89, 10.1006/mcne.1996.0007 Shen, 2011, Age-related changes in myelin morphology, electrophysiological property and myelin-associated protein expression of mouse sciatic nerves, Neurosci Lett, 502, 162, 10.1016/j.neulet.2011.07.034 Sun, 2004, Myelin-associated glycoprotein (Siglec-4) expression is progressively and selectively decreased in the brains of mice lacking complex gangliosides, Glycobiology, 14, 851, 10.1093/glycob/cwh107 Xu, 2014, Peripheral surgical wounding and age-dependent neuroinflammation in mice, PLoS One, 9 Mizuno, 2016, Network analysis of a comprehensive knowledge repository reveals a dual role for ceramide in Alzheimer's disease, PLoS One, 11, 10.1371/journal.pone.0148431 Komohara, 2017, Possible functions of CD169-positive sinus macrophages in lymph nodes in anti-tumor immune responses, Cancer Sci, 108, 290, 10.1111/cas.13137 Black, 2016, The CD169 sialoadhesin molecule mediates cytotoxic T-cell responses to tumour apoptotic vesicles, Immunol Cell Biol, 94, 430, 10.1038/icb.2015.111 Li, 2015, A higher frequency of CD14+ CD169+ monocytes/macrophages in patients with colorectal cancer, PLoS One, 10 Meyer, 2018, B Cell Siglecs–News on signaling and its interplay with ligand binding, Front Immunol, 9, 2820, 10.3389/fimmu.2018.02820 Yoshida, 2017, Efficacy of an anti-CD22 antibody-monomethyl auristatin E conjugate in a preclinical xenograft model of precursor B-cell acute lymphoblastic leukemia, Leuk Lymphoma, 58, 1254, 10.1080/10428194.2016.1235273 Herrmann, 2012, CD34+/CD38− stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin, Haematologica, 97, 219, 10.3324/haematol.2010.035006 Balaian, 2006, Cytotoxic activity of gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia correlates with the expression of protein kinase Syk, Leukemia, 20, 2093, 10.1038/sj.leu.2404437 Liu, 2012, Therapeutic potential of perineural invasion, hypoxia and desmoplasia in pancreatic cancer, Curr Pharm Des, 18, 2395, 10.2174/13816128112092395 Shao, 2016, Siglec-7 defines a highly functional natural killer cell subset and inhibits cell-mediated activities, Scand J Immunol, 84, 182, 10.1111/sji.12455 Läubli, 2014, Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer, Proc Natl Acad Sci USA, 111, 14211, 10.1073/pnas.1409580111 Stanczak, 2018, Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells, J Clin Invest, 128, 4912, 10.1172/JCI120612 Mitra, 2011, SIGLEC12, a human-specific segregating (Pseudo) gene, encodes a signaling molecule expressed in prostate carcinomas, J Biol Chem, 286, 23003, 10.1074/jbc.M111.244152 O'Reilly, 2009, Siglecs as targets for therapy in immune cell mediated disease, Trends Pharmacol Sci, 30, 240, 10.1016/j.tips.2009.02.005 Angata, 2015, Therapeutic targeting of Siglecs using antibody- and glycan-based approaches, Trends Pharmacol Sci, 36, 645, 10.1016/j.tips.2015.06.008 Kawasaki, 2013, Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation, Proc Natl Acad Sci USA, 110, 7826, 10.1073/pnas.1219888110 De Schryver, 2017, Comparative analysis of the internalization of the macrophage receptor sialoadhesin in human and mouse primary macrophages and cell lines, Immunobiology, 222, 797, 10.1016/j.imbio.2016.11.013 Chen, 2012, Antigen delivery to macrophages using liposomal nanoparticles targeting sialoadhesin/CD169, PLoS One, 7 Büll, 2016, Sialic acid mimetics to target the sialic acid-Siglec axis, Trends Biochem Sci, 41, 519, 10.1016/j.tibs.2016.03.007 Macauley, 2013, Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis, J Clin Invest, 123, 3074, 10.1172/JCI69187 Chang, 2015, Extensive crosslinking of CD22 by epratuzumab triggers BCR signaling and caspase-dependent apoptosis in human lymphoma cells, MAbs, 7, 199, 10.4161/19420862.2014.979081 Bera, 2014, An improved recombinant Fab-immunotoxin targeting CD22 expressing malignancies, Leuk Res, 38, 1224, 10.1016/j.leukres.2014.06.014 Bachanova, 2015, Phase I study of a bispecific ligand-directed toxin targeting CD22 and CD19 (DT2219) for refractory B-cell malignancies, Clin Cancer Res, 21, 1267, 10.1158/1078-0432.CCR-14-2877 2017, Anti-CD22 CAR therapy leads to ALL remissions, Cancer Discov, 7, 120, 10.1158/2159-8290.CD-NB2017-001 Loke, 2015, Mylotarg has potent anti-leukaemic effect: a systematic review and meta-analysis of anti-CD33 antibody treatment in acute myeloid leukaemia, Ann Hematol, 94, 361, 10.1007/s00277-014-2218-6 Reusch, 2016, Characterization of CD33/CD3 tetravalent bispecific tandem diabodies (TandAbs) for the treatment of acute myeloid leukemia, Clin Cancer Res, 22, 5829, 10.1158/1078-0432.CCR-16-0350 Cartellieri, 2016, Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts, Blood Cancer J, 6, e458, 10.1038/bcj.2016.61 Aliperta, 2017, Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy, Sci Rep, 7, 42855, 10.1038/srep42855 Griciuc, 2013, Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta, Neuron, 78, 631, 10.1016/j.neuron.2013.04.014 Irving, 2005, Identification of neuroprotective properties of anti-MAG antibody: a novel approach for the treatment of stroke?, J Cereb Blood Flow Metab, 25, 98, 10.1038/sj.jcbfm.9600011 Schachner, 2000, Multiple functions of the myelin-associated glycoprotein MAG (siglec-4a) in formation and maintenance of myelin, Glia, 29, 154, 10.1002/(SICI)1098-1136(20000115)29:2<154::AID-GLIA9>3.0.CO;2-3 Cramer, 2013, MAG111539 Study Investigators. Safety, pharmacokinetics, and pharmacodynamics of escalating repeat doses of GSK249320 in patients with stroke, Stroke, 44, 1337, 10.1161/STROKEAHA.111.674366 Cash, 2016, GSK249320, a monoclonal antibody against the axon outgrowth inhibition molecule myelin-associated glycoprotein, improves outcome of rodents with experimental stroke, J Neurol Exp Neurosci, 2, 28 Blixt, 2003, Sialoside specificity of the Siglec family assessed using novel multivalent probes: identification of potent inhibitors of myelin associated glycoprotein, J Biol Chem, 278, 31007, 10.1074/jbc.M304331200 Yamanaka, 2009, Deletion polymorphism of SIGLEC14 and its functional implications, Glycobiology, 19, 841, 10.1093/glycob/cwp052 Yasui, 2011, Detection of anti-Siglec-14 alloantibodies in blood components implicated in nonhaemolytic transfusion reactions, Br J Haematol, 153, 794, 10.1111/j.1365-2141.2010.08488.x Patel, 1999, OB-BP1/Siglec-6, a leptin- and sialic acid-binding protein of the immunoglobulin superfamily, J Biol Chem, 274, 22729, 10.1074/jbc.274.32.22729 Karl Nocka, Sudhir Rao. Mast cell activation using Siglec-6 antibodies. Patent: US 20060269556 A1. Rumer, 2013, Siglec-6 expression is increased in placentas from pregnancies complicated by preterm preeclampsia, Reprod Sci, 20, 646, 10.1177/1933719112461185 Nicolr, 2003, Ganglioside GD3 expression on target cells can modulate NK cell cytotoxicity via siglec-7-dependent and -independent mechanisms, Eur J Immunol, 33, 1642, 10.1002/eji.200323693 Kawasaki, 2014, Targeted delivery of mycobacterial antigens to human dendritic cells via Siglec-7 induces robust T cell activation, J Immunol, 193, 1560, 10.4049/jimmunol.1303278 Spence, 2015, Targeting Siglecs with a sialic acid-decorated nanoparticle abrogates inflammation, Sci Transl Med, 7, 303ra140, 10.1126/scitranslmed.aab3459 Rubinstein, 2011, Siglec-F inhibition reduces esophageal eosinophilia and angiogenesis in a mouse model of eosinophilic esophagitis, J Pediatr Gastroenterol Nutr, 53, 409, 10.1097/MPG.0b013e3182182ff8 Falahati, 2015, A recombinant antibody to Siglec-8 shows selective ADCC activity against mast cells from systemic mastocytosis patients, Blood, 126, 4092, 10.1182/blood.V126.23.4092.4092 Kiwamoto, 2012, Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions, Pharmacol Ther, 135, 327, 10.1016/j.pharmthera.2012.06.005 von Gunten, 2007, Intravenous immunoglobulin preparations contain anti-Siglec-8 autoantibodies, J Allergy Clin Immunol, 119, 1005, 10.1016/j.jaci.2007.01.023 Schaub, 2011, Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes, Allergy, 66, 1030, 10.1111/j.1398-9995.2011.02579.x Zhang, 2015, Siglec-10 is associated with survival and natural killer cell dysfunction in hepatocellular carcinoma, J Surg Res, 194, 107, 10.1016/j.jss.2014.09.035 Toubai, 2014, Siglec-G-CD24 axis controls the severity of graft-versus-host disease in mice, Blood, 123, 3512, 10.1182/blood-2013-12-545335 Wang, 2010, Alleviation of neurotoxicity by microglial human Siglec-11, J Neurosci, 30, 3482, 10.1523/JNEUROSCI.3940-09.2010 Shahraz, 2015, Anti-inflammatory activity of low molecular weight polysialic acid on human macrophages, Sci Rep, 5, 16800, 10.1038/srep16800 McDonough, 2013, Pharmacogenomic association of nonsynonymous SNPs in SIGLEC12, A1BG, and the selectin region and cardiovascular outcomes, Hypertension, 62, 48, 10.1161/HYPERTENSIONAHA.111.00823 Kameda, 2015, Siglec-15 is a potential therapeutic target for postmenopausal osteoporosis, Bone, 71, 217, 10.1016/j.bone.2014.10.027 Stuible, 2014, Mechanism and function of monoclonal antibodies targeting Siglec-15 for therapeutic inhibition of osteoclastic bone resorption, J Biol Chem, 289, 6498, 10.1074/jbc.M113.494542 Clowse, 2017, Efficacy and safety of epratuzumab in moderately to severely active Systemic Lupus Erythematosus: results from two phase III randomized, double-blind, placebo-controlled trials, Arthritis Rheumatol, 69, 362, 10.1002/art.39856 Raetz, 2008, Children's Oncology Group Pilot Study. Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: a Children's Oncology Group pilot study, J Clin Oncol, 26, 3756, 10.1200/JCO.2007.15.3528 Kantarjian, 2016, Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia, N Engl J Med, 375, 740, 10.1056/NEJMoa1509277 Witzig, 2014, Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma, Haematologica, 99, 1738, 10.3324/haematol.2014.112110 Wayne, 2017, Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia, Blood, 130, 1620, 10.1182/blood-2017-02-749101 Wang, 2017, New development in CAR-T cell therapy, J Hematol Oncol, 10, 53, 10.1186/s13045-017-0423-1 Masonic Cancer Center, University of Minnesota Petersdorf, 2013, A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia, Blood, 121, 4854, 10.1182/blood-2013-01-466706 Hills, 2014, Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials, Lancet Oncol, 15, 986, 10.1016/S1470-2045(14)70281-5 Raza, 2009, Complete remissions observed in acute myeloid leukemia following prolonged exposure to lintuzumab: a phase 1 trial, Leuk Lymphoma, 50, 1336, 10.1080/10428190903050013 Romain, 2014, Antibody Fc engineering improves frequency and promotes kinetic boosting of serial killingmediated by NK cells, Blood, 124, 3241, 10.1182/blood-2014-04-569061 University of Minnesota Rasmussen HS, Chang AT, Tomasevic N, Bebbington CA. Randomized, double-blind, placebo-controlled, ascending dose phase 1 study of AK002, a novel Siglec-8 selective monoclonal antibody, in healthy subjects. J Allergy Clin Immunol 141;2 Suppl.: AB403. Turku University Beatson, 2016, The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9, Nat Immunol, 17, 1273, 10.1038/ni.3552 Bénac, 2018, Preclinical development of first-in-class antibodies targeting Siglec-9 immune checkpoint for cancer immunotherapy [abstract], vol. 78 Guangchao Cao, 2019, Normalization cancer immunotherapy: blocking siglec-15!, Signal Transduct Target Ther, 4, 10, 10.1038/s41392-019-0045-x Wang, 2019, Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy, Nat Med, 25, 656, 10.1038/s41591-019-0374-x Magorivska, 2016, Sialylation of anti-histone immunoglobulin G autoantibodies determines their capabilities to participate in the clearance of late apoptotic cells, Clin Exp Immunol, 184, 110, 10.1111/cei.12744 Chang, 2012, Leukocyte inflammatory responses provoked by Pneumococcal sialidase, MBio, 3, 10.1128/mBio.00220-11 Chen, 2011, Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-Siglec G interaction, Nat Biotechn, 29, 428, 10.1038/nbt.1846 Ohmi, 2016, Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis, Nat Commun, 7, 11205, 10.1038/ncomms11205 Zhang, 2009, Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils, Immunity, 31, 761, 10.1016/j.immuni.2009.09.016 Guzmán-Beltrán, 2013, Nordihydroguaiaretic acid attenuates the oxidative stress-induced decrease of CD33 expression in human monocytes, Oxid Med Cell Longev, 2013, 375893, 10.1155/2013/375893 Sakamoto, 2019, Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis, Nat Chem Biol, 15, 699, 10.1038/s41589-019-0274-x