GM-CSF as a target in inflammatory/autoimmune disease: Current evidence and future therapeutic potential

Expert Review of Clinical Immunology

Volumn 11, Issue 4, 2015, Pages 457-465

  Hamilton, John A ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

antibody; GM CSF; inflammation; KB003; mavrilimumab; MOR103; namilumab; rheumatoid arthritis

Indexed keywords

GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR RECEPTOR; KB 003; MAVRILIMUMAB; MOR 103; MOR BA 022; NAMILUMAB; UNCLASSIFIED DRUG; AUTACOID; MONOCLONAL ANTIBODY;

ASTHMA; AUTOIMMUNE DISEASE; B LYMPHOCYTE; CELL DIFFERENTIATION; CELL POPULATION; CELL SURVIVAL; DENDRITIC CELL; DRUG EFFICACY; DRUG MONITORING; DRUG TARGETING; HELPER CELL; HUMAN; INFLAMMATORY DISEASE; LYMPHOID CELL; MACROPHAGE; MULTIPLE SCLEROSIS; OSTEOCLASTOGENESIS; PHASE 2 CLINICAL TRIAL (TOPIC); REVIEW; RHEUMATOID ARTHRITIS; UNSPECIFIED SIDE EFFECT; ANIMAL; ARTHRITIS, RHEUMATOID; DISEASE MODEL; GENETICS; IMMUNOLOGY; KNOCKOUT MOUSE; METABOLISM; MOUSE;

ANIMALS; ANTIBODIES, MONOCLONAL; ARTHRITIS, RHEUMATOID; CLINICAL TRIALS, PHASE II AS TOPIC; DISEASE MODELS, ANIMAL; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; HUMANS; INFLAMMATION MEDIATORS; MICE; MICE, KNOCKOUT;

EID: 84924982454     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1586/1744666X.2015.1024110     Document Type: Review

References (102)

1. Hamilton JA. GM-CSF in inflammation and autoimmunity. Trends Immunol 2002; 23(8):403-8
2. Hamilton JA, Anderson GP. GM-CSF biology. Growth Factors 2004;22(4):225-31
3. Fleetwood AJ, Cook AD, Hamilton JA. Functions of granulocyte-macrophage colony-stimulating factor. Crit Rev Immunol 2005;25(5):405-28
4. Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 2008;8(7):533-44
5. Cornish AL, Campbell IK, McKenzie BS, et al. G-CSF and GM-CSF as therapeutic targets in rheumatoid arthritis. Nat Rev Rheumatol 2009;5(10):554-9
6. Hamilton JA, Achuthan A. Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol 2013;34(2):81-9
7. van Nieuwenhuijze A, Koenders M, Roeleveld D, et al. GM-CSF as a therapeutic target in inflammatory diseases. Mol Immunol 2013;56(4):675-82
8. Hamilton JA, Stanley ER, Burgess AW, Shadduck RK. Stimulation of macrophage plasminogen activator activity by colony-stimulating factors. J Cell Physiol 1980;103(3):435-45
9. Handman E, Burgess AW. Stimulation by granulocyte-macrophage colony-stimulating factor of Leishmania tropica killing by macrophages. J Immunol 1979;122(3): 1134-7
10. Whetton AD, Dexter TM. Effect of haematopoietic cell growth factor on intracellular ATP levels. Nature 1983; 303(5918):629-31
11. Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 1992; 176(6):1693-702
12. Stanley E, Lieschke GJ, Grail D, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci USA 1994;91(12):5592-6
13. Bogunovic M, Ginhoux F, Helft J, et al. Origin of the lamina propria dendritic cell network. Immunity 2009;31(3):513-25
14. King IL, Kroenke MA, Segal BM. GM-CSF-dependent, CD103+ dermal dendritic cells play a critical role in Th effector cell differentiation after subcutaneous immunization. J Exp Med 2010;207(5):953-61
15. Zhan Y, Carrington EM, van Nieuwenhuijze A, et al. GM-CSF increases cross-presentation and CD103 expression by mouse CD8 spleen dendritic cells. Eur J Immunol 2011;41(9): 2585-95
16. Ghirelli C, Zollinger R, Soumelis V. Systematic cytokine receptor profiling reveals GM-CSF as a novel TLR-independent activator of human plasmacytoid predendritic cells. Blood 2010; 115(24):5037-40
17. Min L, Mohammad Isa SA, Shuai W, et al. Cutting edge: granulocyte-macrophage colony-stimulating factor is the major CD8+T cell-derived licensing factor for dendritic cell activation. J Immunol 2010;184(9): 4625-9
18. Hansen G, Hercus TR, McClure BJ, et al. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 2008;134(3): 496-507
19. Hercus TR, Thomas D, Guthridge MA, et al. The granulocyte-macrophage colonystimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood 2009;114(7):1289-98
20. van De Laar L, Coffer PJ, Woltman AM. Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy. Blood 2012;119(15):3383-93
21. Satwani P, Kahn J, Dvorak CC. Juvenile myelomonocytic leukemia. Pediatr Clin North Am 2015;62(1):95-106
22. Schweizerhof M, Stosser S, Kurejova M, et al. Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain. Nat Med 2009;15(7): 802-7
23. Reed JA, Clegg DJ, Smith KB, et al. GM-CSF action in the CNS decreases food intake and body weight. J Clin Invest 2005; 115(11):3035-44
24. Wang Y, Han G, Wang K, et al. Tumor-derived GM-CSF promotes inflammatory colon carcinogenesis via stimulating epithelial release of VEGF. Cancer Res 2014;74(3):716-26
25. Hamilton JA. A colony-stimulating factor network involving mononuclear phagocytes and other cells. In: Furth VR, editor. Haematopoietic growth factors and mononuclear phagocytes. Karger, Basel; 1993. p. 29-35
26. Hamilton JA. Rheumatoid arthritis: opposing actions of haemopoietic growth factors and slow-acting anti-rheumatic drugs. Lancet 1993;342(8870):536-9
27. Codarri L, Gyulveszi G, Tosevski V, et al. RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011;12(6):560-7
28. Sonderegger I, Iezzi G, Maier R, et al. GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival. J Exp Med 2008; 205(10):2281-94
29. Wu L, Ong S, Talor MV, et al. Cardiac fibroblasts mediate IL-17A-driven inflammatory dilated cardiomyopathy. J Exp Med 2014;211(7):1449-64
30. Su S, Liu Q, Chen J, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 2014; 25(5):605-20
31. Greter M, Helft J, Chow A, et al. GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells. Immunity 2012;36(6):1031-46
32. Edelson BT, Bradstreet TR, Kc W, et al. Batf3-dependent CD11b (low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization. PLoS One 2011;6(10):e25660
33. Jiao Z, Bedoui S, Brady JL, et al. The closely related CD103+ dendritic cells (DCs) and lymphoid-resident CD8+ DCs differ in their inflammatory functions. PLoS One 2014;9(3):e91126
34. Campbell IK, van Nieuwenhuijze A, Segura E, et al. Differentiation of inflammatory dendritic cells is mediated by NF-kappaB1-dependent GM-CSF production in CD4 T cells. J Immunol 2011;186(9):5468-77
35. Ko HJ, Brady JL, Ryg-Cornejo V, et al. GM-CSF-responsive monocyte-derived dendritic cells are pivotal in Th17 pathogenesis. J Immunol 2014; 192(5):2202-9
36. Naik SH, Metcalf D, van Nieuwenhuijze A, et al. Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol 2006;7(6):663-71
37. Zhan Y, Xu Y, Lew AM. The regulation of the development and function of dendritic cell subsets by GM-CSF: more than a hematopoietic growth factor. Mol Immunol 2012;52(1):30-7
38. Mortha A, Chudnovskiy A, Hashimoto D, et al. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 2014; 343(6178):1249288
39. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003;3(1): 23-35
40. Krausgruber T, Blazek K, Smallie T, et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol 2011;12(3):231-8
41. Fleetwood AJ, Lawrence T, Hamilton JA, Cook AD. GM-CSF and M-CSF (CSF-1)- dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities - implications for CSF blockade in inflammation. J Immunol 2007;178(8):5245-52
42. Verreck FA, De Boer T, Langenberg DM, et al. Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc Natl Acad Sci USA 2004;101(13):4560-5
43. Cates AM, Holden VI, Myers EM, et al. Interleukin 10 hampers endothelial cell differentiation and enhances the effects of interferon alpha on lupus endothelial cell progenitors. Rheumatology (Oxford) 2014
44. Willart MA, Deswarte K, Pouliot P, et al. Interleukin-1alpha controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33. J Exp Med 2012;209(8):1505-17
45. Fleetwood AJ, Dinh H, Cook AD, et al. GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on type I interferon signaling. J Leukoc Biol 2009;86(2):411-21
46. Lacey DC, Achuthan A, Fleetwood AJ, et al. Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models. J Immunol 2012;188(11):5752-65
47. Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014;41(1):14-20
48. Lari R, Fleetwood AJ, Kitchener PD, et al. Macrophage lineage phenotypes and osteoclastogenesis-complexity in the control by GM-CSF and TGF-beta. Bone 2007; 40(2):323-36
49. Nomura K, Kuroda S, Yoshikawa H, Tomita T. Inflammatory osteoclastogenesis can be induced by GM-CSF and activated under TNF immunity. Biochem Biophys Res Commun 2008;367(4):881-7
50. Atanga E, Dolder S, Dauwalder T, et al. TNFalpha inhibits the development of osteoclasts through osteoblast-derived GM-CSF. Bone 2011;49(5):1090-100
51. Zaiss MM, Kurowska-Stolarska M, Bohm C, et al. IL-33 shifts the balance from osteoclast to alternatively activated macrophage differentiation and protects from TNF-alpha-mediated bone loss. J Immunol 2011;186(11):6097-105
52. Lee MS, Kim HS, Yeon JT, et al. GM-CSF regulates fusion of mononuclear osteoclasts into bone-resorbing osteoclasts by activating the Ras/ERK pathway. J Immunol 2009; 183(5):3390-9
53. El-Behi M, Ciric B, Dai H, et al. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011;12(6):568-75
54. Sheng W, Yang F, Zhou Y, et al. STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation. Cell Res 2014;24(12): 1387-402
55. Noster R, Riedel R, Mashreghi MF, et al. IL-17 and GM-CSF expression are antagonistically regulated by human T helper cells. Sci Transl Med 2014; 6(241):241ra280
56. Rauch PJ, Chudnovskiy A, Robbins CS, et al. Innate response activator B cells protect against microbial sepsis. Science 2012;335(6068):597-601
57. Weber GF, Chousterman BG, Hilgendorf I, et al. Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis. J Exp Med 2014; 211(6):1243-56
58. Hilgendorf I, Theurl I, Gerhardt LM, et al. Innate response activator B cells aggravate atherosclerosis by stimulating T helper-1 adaptive immunity. Circulation 2014;129(16):1677-87
59. Magri G, Miyajima M, Bascones S, et al. Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells. Nat Immunol 2014;15(4):354-64
60. Robertson SA, Roberts CT, Farr KL, et al. Fertility impairment in granulocyte-macrophage colony-stimulating factor-deficient mice. Biol Reprod 1999; 60(2):251-61
61. Hamilton JA, Davis J, Pobjoy J, Cook AD. GM-CSF is not essential for optimal fertility or for weight control. Cytokine 2012;57(1):30-1
62. Kim DH, Sandoval D, Reed JA, et al. The role of GM-CSF in adipose tissue inflammation. Am J Physiol Endocrinol Metab 2008;295(5):E1038-46
63. Hazenberg BP, Van Leeuwen MA, Van Rijswijk MH, et al. Correction of granulocytopenia in Feltys syndrome by granulocyte-macrophage colony-stimulating factor. Simultaneous induction of interleukin-6 release and flare-up of the arthritis. Blood 1989;74(8):2769-70
64. Campbell IK, Bendele A, Smith DA, Hamilton JA. Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice. Ann Rheum Dis 1997;56(6):364-8
65. Lang RA, Metcalf D, Cuthbertson RA, et al. Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. Cell 1987;51(4):675-86
66. van Nieuwenhuijze AE, Coghill E, Gray D, et al. Transgenic expression of GM-CSF in T cells causes disseminated histiocytosis. Am J Pathol 2014;184(1):184-99
67. Llop-Guevara A, Chu DK, Walker TD, et al. A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure. PLoS ONE 2014;9(2):e88714
68. Egea L, Hirata Y, Kagnoff MF. GM-CSF: a role in immune and inflammatory reactions in the intestine. Expert Rev Gastroenterol Hepatol 2010;4(6):723-31
69. Roth L, Macdonald JK, McDonald JW, Chande N. Sargramostim (GM-CSF) for induction of remission in Crohns disease: a cochrane inflammatory bowel disease and functional bowel disorders systematic review of randomized trials. Inflamm Bowel Dis 2012;18(7):1333-9
70. Campbell IK, Rich MJ, Bischof RJ, et al. Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice. J Immunol 1998; 161(7):3639-44
71. McQualter JL, Darwiche R, Ewing C, et al. Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. J Exp Med 2001;194(7): 873-82
72. Shiomi A, Usui T, Ishikawa Y, et al. GM-CSF but not IL-17 is critical for the development of severe interstitial lung disease in SKG mice. J Immunol 2014; 193(2):849-59
73. Ye P, Chen W, Wu J, et al. GM-CSF contributes to aortic aneurysms resulting from SMAD3 deficiency. J Clin Invest 2013;123(5):2317-31
74. Samavedam UK, Iwata H, Muller S, et al. GM-CSF modulates autoantibody production and skin blistering in experimental epidermolysis bullosa acquisita. J Immunol 2014;192(2):559-71
75. Greven DE, Cohen ES, Gerlag DM, et al. Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis. Ann Rheum Dis 2014. [Epub ahead of print
76. Khajah M, Millen B, Cara DC, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF): a chemoattractive agent for murine leukocytes in vivo. J Leukoc Biol 2011;89(6):945-53
77. Griseri T, McKenzie BS, Schiering C, Powrie F. Dysregulated hematopoietic stem and progenitor cell activity promotes interleukin-23-driven chronic intestinal inflammation. Immunity 2012;37(6): 1116-29
78. Brosbol-Ravnborg A, Hvas CL, Agnholt J, et al. Toll-like receptor-induced granulocytemacrophage colony-stimulating factor secretion is impaired in Crohns disease by nucleotide oligomerization domain 2-dependent and -independent pathways. Clin Exp Immunol 2009;155(3):487-95
79. Dabritz J. Granulocyte macrophage colony-stimulating factor and the intestinal innate immune cell homeostasis in Crohns disease. Am J Physiol Gastrointest Liver Physiol 2014;306(6):G455-65
80. A single dose study of the CAM-3001 in patients with rheumatoid arthritis. Available from: https://clinicaltrials.gov/ct2/show/NCT00771420
81. Burmester GR, Feist E, Sleeman MA, et al. Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-alpha, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study. Ann Rheum Dis 2011;70(9):1542-9
82. A study to evaluate the efficacy and safety of CAM-3001 (Drug) in subjects with rheumatoid arthritis. Available from: https://clinicaltrials.gov/ct2/show/NCT01050998
83. Burmester GR, Weinblatt ME, McInnes IB, et al. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis 2013;72(9):1445-52
84. A study of mavrilimumab in subjects with moderate-to-severe rheumatoid arthritis. Available from: https://clinicaltrials.gov/ct2/show/NCT01706926
85. Burmester G, McInnes IB, Kremer JM, et al. Efficacy and safety/tolerability of mavrilimumab, a human GM-CSFRÃ monoclonal antibody in patients with rheumatoid arthritis. In: American College of Rheumatology. Wiley; Boston: 2014
86. McInnes IB, Burmester GR, Kremer JM, et al. Rapid onset of clinical benefit is associated with a reduction in validated biomarkers of disease in patients with rheumatoid arthritis treated with mavrilimumab, a human monoclonal antibody targeting GM-CSFRÃ In: Amercian College of Rheumatology Wiley; Boston: 2014
87. Kremer JM, Burmester G, Weinblatt M, et al. Analysis of patient-reported outcomes during treatment with mavrilimumab, a human monoclonal antibody targeting GM-CSFRá, in the randomized Phase 2b Earth Explorer 1 Study. In: Amercan College of Rheumatology Wiley; Boston: 2014
88. Di Franco M, Gerardi MC, Lucchino B, Conti F. Mavrilimumab: an evidence based review of its potential in the treatment of rheumatoid arthritis. Core Evid 2014;9:41-8
89. A long term safety study of mavrilimumab in adult subjects with rheumatoid arthritis. Available from: https://clinicaltrials.gov/ct2/show/NCT01712399
90. A study of mavrilimumab versus anti tumor necrosis factor in subjects with rheumatoid arthritis. Available from: www.clinicaltrials. gov/ct2/show/NCT01715896
91. Safety and preliminary efficacy of MOR103 in patients with active rheumatoid arthritis. Available from: https://clinicaltrials.gov/ct2/show/NCT01023256
92. Behrens F, Tak PP, Ostergaard M, et al. MOR103, a human monoclonal antibody to granulocyte-macrophage colonystimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis 2014. [Epub ahead of print
93. Phase Ib study to evaluate MOR103 in multiple sclerosis. Available form https://clinicaltrials.gov/ct2/show/NCT01517282
94. Constantinescu C, Asher A, Fryze W, et al. Safety and pharmacokinetics of MOR103, a human antibody to granulocyte-macrophage colony-stimulating factor, in patients with multiple sclerosis. Multiple Sclerosis 2014; 20(1 Suppl):4-66
95. Study of KB003 in biologics-inadequate rheumatoid arthritis. Available from: https://clinicaltrials.gov/ct2/show/NCT00995449
96. Effect of KB003 in subjects with asthma inadequately controlled by corticosteroids (KB003-04). Available from: https://clinicaltrials.gov/ct2/show/NCT01603277
97. A trial to evaluate the safety and tolerability of mt203 in patients with mild to moderate rheumatoid arthritis (PRIORA). Available from: https://clinicaltrials.gov/ct2/show/NCT01317797
98. Efficacy and safety of namilumab (MT203) for plaque psoriasis. Available from: https://clinicaltrials.gov/ct2/show/NCT02129777
99. Safety and tolerability of MORAb-022 in healthy and rheumatoid arthritis subjects. Available from: https://clinicaltrials.gov/ct2/show/NCT01357759
100. Spight D, Trapnell B, Zhao B, et al. Granulocyte-macrophage-colony-stimulating factor-dependent peritoneal macrophage responses determine survival in experimentally induced peritonitis and sepsis in mice. Shock 2008;30(4):434-42
101. Cook AD, Pobjoy J, Sarros S, et al. Granulocyte-macrophage colony-stimulating factor is a key mediator in inflammatory and arthritic pain. Ann Rheum Dis 2013; 72(2):265-70
102. A double-blind, placebo-controlled, single-dose study to evaluate the PK, IM, and safety in Japanese subjects. Available from: https://clinicaltrials.gov/ct2/show/NCT02213315