Development of Effective Siglec-9 Antibodies Against Cancer

Angata T, Varki A. Cloning, characterization, and phylogenetic analysis of Siglec-9, a new member of the CD33-related group of Siglecs: evidence for co-evolution with sialic acid synthesis pathways. J Biol Chem. 2000;275:22127–35.

Article  PubMed  CAS  Google Scholar 

Zhang JQ, Nicoll G, Jones C, Crocker PR. Siglec-9, a novel sialic acid binding member of the immunoglobulin superfamily expressed broadly on human blood leukocytes. J Biol Chem. 2000;275:22121–6.

Article  PubMed  CAS  Google Scholar 

Avril T, Floyd H, Lopez F, Vivier E, Crocker PR. The membrane-proximal immunoreceptor tyrosine-based inhibitory motif is critical for the inhibitory signaling mediated by Siglecs-7 and -9, CD33-related Siglecs expressed on human monocytes and NK cells. J Immunol Am Assoc Immunol. 2004;173:6841–9.

CAS  Google Scholar 

Jandus C, Boligan KF, Chijioke O, Liu H, Dahlhaus M, Démoulins T, et al. Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. J Clin Inv Am Soc Clin Inv. 2014;124:1810–20.

Article  CAS  Google Scholar 

Lizcano A, Secundino I, Dohrmann S, Corriden R, Rohena C, Diaz S, et al. Erythrocyte sialoglycoproteins engage Siglec-9 on neutrophils to suppress activation. Blood Am Soc Hematol. 2017;129:3100–10.

CAS  Google Scholar 

•• Haas Q, Boligan KF, Jandus C, Schneider C, Simillion C, Stanczak MA, et al. Siglec-9 regulates an effector memory CD8+ T-cell subset that congregates in the melanoma tumor microenvironment. Cancer Immunol Res. American Association for Cancer Research Inc. 2019;7:707–18. This study highlights a combinatorial approach using both anti-Siglec-9 and anti-PD-1 to enhance CD8+ T cell cytotoxicity.

•• Rosenthal Arnon, Monroe Kate, Lee Seung-Joo. Anti-siglec-9 antibodies and methods of use thereof. Patent US20210095023A1. 2021. This study describes the use of CLIPS technology to map conformational epitopes recognized by anti-Siglec-9 clones 2D4, 2D5, 191240, E10–286, and 5C6.

Gonzalez-Gil A, Schnaar RL. Siglec ligands. Cells. 2021;10:1260.

Stanczak MA, Siddiqui SS, Trefny MP, Thommen DS, Boligan KF, von Gunten S, et al. Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells. J Clin Inv Am Soc Clin Inv. 2018;128:4912–23.

Article  Google Scholar 

Belisle JA, Horibata S, Jennifer GA, et al. Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes. Mol Cancer. 2010;9:118.

Läubli H, Pearce OMT, Schwarz F, Siddiqui SS, Deng L, Stanczak MA, et al. Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer. Proc Natl Acad Sci U S A. National Academy of Sciences. 2014;111:14211–6.

Ibarlucea-Benitez I, Weitzenfeld P, Smith P, Ravetch J v. Siglecs-7/9 function as inhibitory immune checkpoints in vivo and can be targeted to enhance therapeutic antitumor immunity. Proc Natl Acad Sci U S A [Internet]. 2021;118.

Beatson R, Tajadura-Ortega V, Achkova D, Picco G, Tsourouktsoglou TD, Klausing S, et al. The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. Nat Immunol Nature Publishing Group. 2016;17:1273–81.

Article  CAS  Google Scholar 

• Beatson R, Graham R, Grundland Freile F, et al. Cancer-associated hypersialylated MUC1 drives the differentiation of human monocytes into macrophages with a pathogenic phenotype. Commun Biol. 2020;3(1):644. This study describes Siglec-9 signaling pathways that drive the formation of TAMs in breast cancer patients.

• Rodriguez E, Boelaars K, Brown K, et al. Sialic acids in pancreatic cancer cells drive tumour associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9. Nat Commun. 2021;12(1):1270. This study describes Siglec-9 signaling pathways that drive the formation of TAMs in pancreatic ductal adenocarcinoma.

Läubli H, Alisson-Silva F, Stanczak MA, Siddiqui SS, Deng L, Verhagen A, et al. Lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is a tumor-associated immunomodulatory ligand for CD33-related siglecs. J Biol Chem Am Soc Biochem Mol Biol Inc. 2014;289:33481–91.

Miyazaki K, Sakuma K, Kawamura YI, Izawa M, Ohmori K, Mitsuki M, et al. Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors Siglec-7 and -9. J Immunol Am Assoc Immunolog. 2012;188:4690–700.

CAS  Google Scholar 

•• Cornen Stéphanie, Rossi Benjamin, Wagtmann Nicolai, Gauthier Laurent. Siglec-9-neutralizing antibodies. Patent US20200369765A1. 2020. This study describes the Siglec-9 blocking antibodies in reducing tumor size in colorectal adenocarcinoma, HT29 cells.

Yamakawa N, Yasuda Y, Yoshimura A, et al. Discovery of a new sialic acid binding region that regulates Siglec-7. Sci Rep. 2020;10(1):8647.

Choi H, Ho M, Adeniji OS, Giron L, Bordoloi D, Kulkarni AJ, Puchalt AP, Abdel-Mohsen M, Muthumani K. Development of Siglec-9 blocking antibody to enhance anti-tumor immunity. Front Oncol. 2021;11:778989.

•• Kar Muthumani, Mohamed Abdel-Mohsen, David Weiner, Shyam Somasundaram. Monoclonal antibodies against Siglec-9 and use thereof for immunotherapy. Patent WO2021247821. 2021. This study describes the Siglec-9 blocking antibodies in promoting NK cell cytotoxicity against chronic myelogenous leukemia, K562 cells.

Yu H, Gonzalez-Gil A, Wei Y, Fernandes SM, Porell RN, Vajn K, et al. Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties. Glycobiology Oxford Univ Press. 2017;27:657–68.

Article  CAS  Google Scholar 

Delaveris CS, Wilk AJ, Riley NM, Stark JC, Yang SS, Rogers AJ, et al. Synthetic Siglec-9 agonists inhibit neutrophil activation associated with COVID-19. ACS Cent Sci Am Chem Soc. 2021;7:650–7.

Article  CAS  Google Scholar 

Kucka K, Wajant H. Receptor oligomerization and its relevance for signaling by receptors of the tumor necrosis factor receptor superfamily. Front Cell Dev Biol. 2021;8:615141.

Han S, Collins BE, Bengtson P, Paulson JC. Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross-linking. Nat Chem Biol. 2005;1:93–7.

Article  PubMed  CAS  Google Scholar 

Cornish AL, Freeman S, Forbes G, et al. Characterization of siglec-5, a novel glycoprotein expressed on myeloid cells related to CD33. Blood. 1998;92(6):2123–32.

Article  PubMed  CAS  Google Scholar 

Floyd H, Ni J, Cornish AL, Zeng Z, Liu D, Carter KC, et al. Siglec-8 A novel eosinophil-specific member of the immunoglobulin superfamily. J Biol Chem. 2000;275:861–6.

Article  PubMed  CAS  Google Scholar 

Angata T, Kerr SC, Greaves DR, Varki NM, Crocker PR, Varki A. Cloning and characterization of human Siglec-11: a recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia. J Biol Chem. 2002;277:24466–74.

Article  PubMed  CAS  Google Scholar 

Nicoll G, Ni J, Liu D, Klenerman P, Munday J, Dubock S, et al. Identification and characterization of a novel siglec, siglec-7, expressed by human natural killer cells and monocytes. J Biol Chem. 1999;274:34089–95.

Article  PubMed  CAS  Google Scholar 

Delaveris CS, Chiu SH, Riley NM, Bertozzi CR. Modulation of immune cell reactivity with CIS binding Siglec agonists. Proc Natl Acad Sci U S A. 2021;118:e2012408118.

Wilson NS, Yang B, Yang A, Loeser S, Marsters S, Lawrence D, et al. An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell Cell Press. 2011;19:101–13.

Article  CAS  Google Scholar 

Carlin AF, Uchiyama S, Chang YC, Lewis AL, Nizet V, Varki A. Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response. Blood. 2009;113(14):3333–6.

Chu S, Zhu X, You N, Zhang W, Zheng F, Cai B, Zhou T, Wang Y, Sun Q, Yang Z, Zhang X, Wang C, Nie S, Zhu J, Wang M. The fab fragment of a human Anti-Siglec-9 monoclonal antibody suppresses LPS-induced inflammatory responses in human macrophages. Front Immunol. 2016;7:649.

Mamat U, Wilke K, Bramhill D, et al. Detoxifying Escherichia coli for endotoxin-free production of recombinant proteins. Microb Cell Fact. 2015;14:57.

von Gunten S, Schaub A, Vogel M, Stadler BM, Miescher S, Simon HU. Immunologic and functional evidence for anti-Siglec-9 autoantibodies in intravenous immunoglobulin preparations. Blood. 2006;108:4255–9.

Article  Google Scholar 

von Gunten S, Yousefi S, Seitz M, Jakob SM, Schaffner T, Seger R, et al. Siglec-9 transduces apoptotic and nonapoptotic death signals into neutrophils depending on the proinflammatory cytokine environment. Blood. 2005;106:1423–31.

Article  Google Scholar 

Biedermann B, Gil D, Bowen DT, Crocker PR. Analysis of the CD33-related siglec family reveals that Siglec-9 is an endocytic receptor expressed on subsets of acute myeloid leukemia cells and absent from normal hematopoietic progenitors. Leuk Res. 2007;31:211–20.

Article  PubMed  CAS  Google Scholar 

Mayes PA, Hance KW, Hoos A. The promise and challenges of immune agonist antibody development in cancer. Nat Rev Drug Discov. 2018;17(7):509–27.

Weiss A, Manger B, Imboden J. Synergy between the T3/antigen receptor complex and Tp44 in the activation of human T cells. J Immunol. 1986;137(3):819–25.

PubMed  CAS  Google Scholar 

Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol. 2002;3(2):135–42.

Kjaergaard J, Tanaka J, Kim JA, Rothchild K, Weinberg A, Shu S. Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res. 2000;60(19):5514–21.

PubMed  CAS  Google Scholar 

Bulliard Y, Jolicoeur R, Zhang J, Dranoff G, Wilson NS, Brogdon JL. OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy. Immunol Cell Biol Nature Publishing Group. 2014;92:475–80.

Article  CAS  Google Scholar 

•• Heinz Laubli, Simone Schmitt, Christoph Esslinger. Anti-Siglec-9 antibody molecules. Patent WO2021094545. 2021. This study describes Siglec-9 blocking antibody which activates CD4+ and CD8+ T cells, as well as increased cytotoxicity of NK92 cell line against chronic myelogenous leukemia, K562 cells. Additionally, they showed that weak binding anti-Siglec-9 clone 5C6 demonstrated no functional activity.

Zhang D, Goldberg MV, Chiu ML. Fc engineering approaches to enhance the agonism and effector functions of an Anti-OX40 antibody. J Biol Chem Am Soc Biochem Mol Biol Inc. 2016;291:27134–46.

Vaddepally RK, Kharel P, Pandey R, Garje R, Chandra AB. Review of indications of FDA approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers (Basel). 2020;12(3):738.

Ahmed SR, Petersen E, Patel R, Migden MR. Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Expert Rev Clin Pharmacol. 2019;12(10):947–51.

Barone A, Hazarika M, Theoret MR, et al. FDA approval summary: pembrolizumab for the treatment of patients with unresectable or metastatic melanoma. Clin Cancer Res. 2017;23(19):5661–5.

Zhang Q, Huo GW, Zhang HZ, Song Y. Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis. Open Med (Wars). 2020;15(1):447–56.

Norsworthy KJ, Ko C-W, Lee JE, Liu J, John CS, Przepiorka D, et al. FDA approval summary: Mylotarg for treatment of patients with relapsed or refractory CD33-positive acute myeloid leukemia. Oncologist Oxford Univ Press (OUP). 2018;23:1103–8.

CAS  Google Scholar 

Xiao H, Woods EC, Vukojicic P, Bertozzi CR. Precision glycocalyx editing as a strategy for cancer immunotherapy. Proc Natl Acad Sci U S A. Natl Acad Sci. 2016;113:10304–9.

• Wu Y, Huang W, Xie Y, Wang C, Luo N, Chen Y, Wang L, Cheng Z, Gao Z, Liu S. Siglec-9, a putative immune checkpoint marker for cancer progression across multiple cancer types. Front Mol Biosci. 2022;9:743515. This study highlights the broad application of Siglec-9 as an immune checkpoint target across various cancers.

Lim J, Puan KJ, Wang LW, et al. Data-driven analysis of COVID-19 reveals persistent immune abnormalities in convalescent severe individuals. Front Immunol. 2021;12:710217.

Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature Nature Research. 2021;596:583–9.

Article  CAS  Google Scholar 

Chodorge M, Züger S, Stirnimann C, Briand C, Jermutus L, Grütter MG, et al. A series of Fas receptor agonist antibodies that demonstrate an inverse correlation between affinity and potency. Cell Death Differ. 2012;19:1187–95.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Hudak JE, Canham SM, Bertozzi CR. Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. Nat Chem Biol Nature Publishing Group. 2014;10:69–75.

Article  CAS  Google Scholar 

Khatua B, Bhattacharya K, Mandal C. Sialoglycoproteins adsorbed by Pseudomonas aeruginosa facilitate their survival by impeding neutrophil extracellular trap through siglec-9. J Leukoc Biol Wiley. 2012;91:641–55.

Article  CAS  Google Scholar 

Rodrigues E, Jung J, Park H, et al. A versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands. Nat Commun. 2020;11:5091.

Mimoto F, Katada H, Kadono S, Igawa T, Kuramochi T, Muraoka M, et al. Engineered antibody Fc variant with selectively enhanced FcγRIIb binding over both FcγRIIaR131 and FcγRIIaH131. Protein Eng Des Sel. 2013;26:589–98.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Diebolder CA, Beurskens FJ, de Jong RN, Koning RI, Strumane K, Lindorfer MA, et al. Complement is activated by IgG hexamers assembled at the cell surface. Science (1979). Am Assoc Adv Sci. 2014;343:1260–3.

留言 (0)

沒有登入
gif