Investigational C-C chemokine receptor 2 antagonists for the treatment of autoimmune diseases

Expert Opinion on Investigational Drugs

Volumn 17, Issue 9, 2008, Pages 1267-1279

  Kalinowska, Alicja ^a   Losy, Jacek ^a,b  

^a POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

^b POLISH ACADEMY OF SCIENCES   (Poland)

Author keywords

Atherosclerosis; Autoimmune diseases; CCR2; CCR2 antagonists; Collagen induced arthritis; Experimental autoimmune encephalomyelitis; MCP 1 CCL2; Multiple sclerosis; Rheumatoid arthritis; Sclerodema systemic sclerosis; Systemic lupus erythematosus

Indexed keywords

7 ND MCP 1; 9 76 MCP 1; ABN 912; ANTIINFLAMMATORY AGENT; BETA CHEMOKINE; BINDING PROTEIN; CCX 915; CHEMOKINE BINDING PROTEIN; CHEMOKINE RECEPTOR AFFECTING AGENT; CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR2 ANTAGONIST; CYCLOPHOSPHAMIDE; IMMUNOMODULATING AGENT; IMMUNOSUPPRESSIVE AGENT; INCB 003284; INCB 3284; INCB 3344; INCB 8696; MK 0812; MLN 1202; MNOX E 36; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY MCP 1; MONOCYTE CHEMOTACTIC PROTEIN 1; OLIGONUCLEOTIDE; PLACEBO; RECEPTOR BLOCKING AGENT; SPIEGELMER; UNCLASSIFIED DRUG;

ATHEROSCLEROSIS; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CELL POLARITY; CELL SURVIVAL; CLINICAL FEATURE; CLINICAL TRIAL; CYTOKINE PRODUCTION; DISEASE COURSE; DISEASE PREDISPOSITION; DRUG DOSAGE FORM COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG INDICATION; DRUG MECHANISM; DRUG MEGADOSE; DRUG RESEARCH; DRUG SAFETY; DRUG SYNTHESIS; DRUG TARGETING; DRUG TOLERABILITY; HELPER CELL; HUMAN; HUMORAL IMMUNITY; IMMUNOPATHOGENESIS; IMMUNOREGULATION; LEUKOCYTE MIGRATION; LOW DRUG DOSE; MULTIPLE SCLEROSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PEER REVIEW; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN MOTIF; PROTEIN TARGETING; RECEPTOR BLOCKING; REGULATORY MECHANISM; REVIEW; RHEUMATOID ARTHRITIS; SCLERODERMA; SYSTEMIC LUPUS ERYTHEMATOSUS; SYSTEMIC SCLEROSIS; T LYMPHOCYTE; TREATMENT OUTCOME;

ANIMALS; AUTOIMMUNE DISEASES; CELL MOVEMENT; CHEMOKINE CCL2; DRUG EVALUATION, PRECLINICAL; HUMANS; PROTEIN BINDING; TREATMENT OUTCOME;

EID: 52949104096     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.17.9.1267     Document Type: Review

References (87)

1. Losy J, Zaremba J. Monocyte chemoattractant protein-1 is increased in the cerebrospinal fluid of patients with ischemic stroke. Stroke 2001;32(11):2695-6
2. Kinne RW, Bäuer R, Stuhlmüller B, et al. Macrophages in rheumatoid arthritis. Arthritis Res 2000;2(3):189-202
3. Brück W, Sommermeier N, Bergmann M, et al. Macrophages in multiple sclerosis. Immunobiology 1996;195(4-5):588-600
4. Anders HJ, Vielhauer V. Identifying and validating novel targets with in vivo disease models: guidelines for study design. Drug Discov Today 2007;12(11-12):446-51
5. Wells TN, Power CA, Shaw JP, Proudfoot AE, Chemokine blockers - therapeutics in the making? Trends Pharmacol Sci 2006;27(1):41-7
6. Goodnow CC. Multistep pathogenesis of autoimmune disease. Cell 2007;130(1):25-35
7. Johnson Z, Schwarz M, Power CA, et al. Multi-faceted strategies to combat disease by interference with the chemokine system. Trends Immunol 2005;26(5):268-74
8. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006;354(6):610-21
9. Rot A, von Andrian UH. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Ann Rev Immunol 2004;22:891-928
10. Moser B, Wolf M, Walz A, Loetscher P. Chemokines: multiple levels of leukocyte migration control. Trends Immunol 2004;25(2):75-84
11. Power CA, Proudfoot AE. The chemokine system: novel broad-spectrum therapeutic targets. Curr Opin Pharmacol 2001;1:417-24
12. Szczucinski A, Losy J. Chemokines and chemokine receptors in multiple sclerosis. Potential targets for new therapies. Acta Neurol Scand 2007; 115(3):137-46
13. Bettelli E, Oukka M, Kuchroo VK. TH-17 cells in the circle of immunity and autoimmunity. Nat Immunol 2007;8(4)345-50.
14. Bettelli E, Korn T, Kuchroo VK. Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 2007;19:652-7
15. Aranami T, Yamamura T. Th17 cells and autoimmune encephalomyelitis (EAE/ MS). Allergol Int 2008;57(2):115-20
16. Sato W, Aranami T, Yamamura T. Cutting edge: human Th17 cells are identified as bearing CCR2+CCR5- phenotype. J Immunol 2007;178(12):7525-9
17. Kebir H, Kreymborg K, Ifergan I, et al. Human T(H)17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 2007;13:1173-5
18. Webb A, Johnson A, Fortunato M, et al. Evidence for PI-3K-dependent migration of Th17-polarized cells in response to CCR2 and CCR6 agonists. J Leukoc Biol Epub 27 June 2008, doi:10.1189/jlb.0408234
19. Boring L, Gosling J, Chensue SW, et al. Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J Clin Invest 1997; 100(10):2552-61
20. Sato N, Kuziel WA, Melby PC, et al. Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice. J Immunol 1999;163(10):5519-25
21. Traynor TR, Kuziel WA, Toews GB, Huffnagle GB. CCR2 expression determines T1 versus T2 polarization during pulmonary Cryptococcus. neoformans infection. J Immunol 2000;164(4):2021-7.
22. Peters W, Dupuis M, Charo IF. A mechansm for the impaired IFN-γ production in C-C chemokine receptor 2 (CCR2) knockout mice: role of CCR2 in linking the innate, and adaptive immune responses. J Immunol 2000; 165(12):7072-7
23. H2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 2000;404(6776):407-11
24. The Pharmaprojects Database, Informa UK Ltd. Available from http://www.pharmaprojects.com
25. Park IK, Hiraki K, Kohyama K, Matsumoto Y. Differential effects of decoy chemokine (7ND) gene therapy on acute, biphasic and chronic autoimmune encephalomyelitis: implication for pathomechanisms of lesion formation. J Neuroimmunol 2008; 194(1-2):34-43
26. Ni W, Egashira K, Kitamoto S, et al. New anti-monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice. Circulation 2001;103(16):2096-101
27. Wada T, Furuichi K, Sakai N, et al. Gene therapy via blockade of monocyte chemoattractant protein-1 for renal fibrosis. J Am Soc Nephrol 2004;15:940-8
28. Moore BB, Paine R III, Christensen PJ, et al. Protection from pulmonary fibrosis in the absence of CCR2 signaling. J Immunol 2001;167(8):4368-77
29. Kitagawa K, Wada T, Furuichi K, et al. Blockade of CCR2 ameliorates progressive fibrosis in kidney. Am J Pathol 2004;165(1):237-46
30. Gong JH, Ratkay LG, Waterfield JD, Clark-Lewis I. An antagonist of monocyte chemoattractant protein I (MCP-1) inhibits arthritis in the MRL-lpr mouse model. J Exp Med 1997;186(1):131-7
31. Liu L, Dai E, Miller L, et al. Viral chemokine-binding proteins inhibit inflammatory responses and aortic allograft transplant vasculopathy in rat models. Transplantation 2004;77(11):1652-60
32. Rowland LP, editor. Merrite's neurology. 11th edition. Philadelpliia, USA: Lippincott Williams & Wilkins; 2005
33. Eltayeb S, Berg AL, Lassmann H, et al. Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE. J Neuroinflamm 2007;4:14
34. Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ. CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 2000;192(6):899-906
35. Ezikson L, Klein RS, Charo IF, et al. Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR2). J Exp Med 2000; 192(7):1075-80
36. Gaupp S, Pitt D, Kuziel WA, et al. Experimental autoimmune encephalomyelitis (EAE) in CCR2-/-mice. Susceptibility in multiple strains. Am J Pathol 2003; 162(1):139-50
37. Brodmerkel CM, Huber R, Covington M, et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist. INCB3344. J Immunol 2005;175(8):5370-8
38. Franciotta D, Martino G, Zardini E, et al. Serum, and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies. J Neuroimmunol 2001; 115:1912-8
39. Sindern E, Niederkinkhaus Y, Henschel M, et al. Differential release of beta-chemokines in serum and CSF of patients with relapsing-remitting multiple sclerosis. Acta Neurol Scand 2001;104:88-91
40. Sorensen TL, Sellebjerg F, Jensen CV, et al. Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis. Eur J Neurol 2001;8:665-72
41. Lahrtz F, Piali L, Nadal D, et al. Chemotactic activity on mononuclear cells in the cerebrospinal fluid of patients with viral meningitis is mediated by interferon-gamma inducible protein-10 and monocyte chemotactic protein-1. Eur J Immunol 1997;27:2484-9
42. Lahrtz F, Piali L, Spanaus KS, et al. Chemokines and chemotaxis of leukocytes in infectious meningitis. J Neuroimmunol 1998;85:33-43
43. Simpson J, Rezaie P, Newcombe J, et al. Expression of the beta-chemokine receptors CCR2, CCR3,and CCR5 in multiple sclerosis central nervous system tissue. J Neuroimmunol 2000;108:192-200
44. Mahad D, Callahan MK, Williams KA, et al. Modulating CCR2 and CCL2 at the blood-brain barrier: relevance for multiple sclerosis pathogenesis. Brain 2006;129:212-23
45. Misu T, Onodera H, Fujihara K, et al. Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis: imbalance of Th1n/Th2-associated chemokine signalling. J Neuroimmunol 2001;114:207-12
46. Kivisaekk P, Trebst C, Liu Z, et al. T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking. Clin Exp Immunol 2002;129:510-8
47. Millennium announces MLN1202 significantly reduced marker of systemic inflammation and identifies genomic biomarker for responders. Millennium, Pharmaceuticals, Inc., 2007. Available from: http://investor.millennium.com/phoenix.zhtml?c=80159&p= irol-newmediaArticle&ID=l073472&highlight= [Last accessed 26 May 2008]
48. A study to assess the effects of MK0812 on disease activity in patients with relapsing-remitting multiple sclerosis as measured by magnetic resonance imaging (MRI). NCT00239655. ClinicalTrials.gov, 2005. Available from http://clinicaltrials.gov/ct2/show/record/NCT00239655 [Last accessed 26 May 2008]
49. Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001;344(12):907-16
50. Quinones MP, Ahuja SK, Jimenez F, et al. Experimental arthritis in CCchemokine receptor 2-null mice closely mimice severe human rheumatoid arthritis. J Clin Invest 2004;113:856-66
51. Tak PP, Smeets TJM, Daha MR, et al. Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity Arthritis Rheum 1997;40:217-25
52. Barrera P, Blom A, van Lent PL, et al. Synovial macrophage depletion with clodronatc-containing liposomes in rheumatoid arthritis. Arthritis Rheum 2000;43(9):1951-9
53. Smeets TJ, Kraan MC, van Loon ME, Tak PP. Tumor necrosis factor alpha blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue. Arthritis Rheum 2003;48:2155-62
54. Plater-Zyberk C, Hoogewerf AJ, Proudfoot AE, et al. Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice. Immunol Lett 1997;57(1-3):117-20
55. Mack M, Brühl H, Gruber R, et al. Predominance of mononuclear cells expressing the chemokine receptor CCR5 in synovial effusions of patients with different forms of arthritis. Arthritis Rheum 1999;42:981-8
56. Brühl H, Wagner K, Kellner H, et al. Surface expression of CC- and CXC-chemokine receptors on leucocyte subsets in inflammatory joint diseases. Clin Exp Immunol 2001;126:551-9
57. Koch AE, Kunkel SL, Hadow LA, et al. Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. J Clin Invest 1992;90:772-9
58. Hayashida K, Nanki T, Girschick H, et al. Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing MCP-1 and IL-8. Arthritis Res 2001;3(2):118-26
59. Ogata H, Takeya M, Youshimura T, et al. The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats. J Pathol 1997;182:106-14
60. Brühl H, Cihak J, Schneider MA, et al. Dual role of CCR2 during initiation and progression of collagen-induced arthritis: evidence for regulatory activity of CCR2+T cells. J Immunol 2004;172:890-8
61. Haringman JJ, Gerlag DM, Smeets TJ, et al. A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis. Arthritis Rheum 2006;54(8):2387-92
62. A placebo-controlled, parallel-group, double-blind, 12-week study to assess the clinical efficacy, safety, and tolerability of MK-0812 in rheumatoid arthritis patients. NCT00542022. ClinicalTrials.gov, 2007. Available from: http://clinicaltrials.gov/ct2/show/ NCT00542022?cond=%22Arthritis%2C+Rheumatoid%22&rank=38 [Last accessed 26 May 2008]
63. Beaulieu A, Hasler F, Martin Mola E, et al. The efficacy and safety of a CCR2 receptor antagonist in the treatment of rheumatoid arthritis (RA). Ann Rheum Dis 2006;65 (Suppl II): 175
64. Vergunst CE, Gerlag DM, Lopatinskaya L, et al. Modulation of CCR2 in rheumatoid arthritis: a double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum 2008;58(7):1931-9
65. Yamamoto T, Eckes B, Krieg T. High expression and autoinduction of monocyte chemoattractant protein-1 in scleroderma fibroblasts. Eur J Immunol 2001;31(10):2936-41
66. Yamamoto T, Eckes B, Hartmann K, Krieg T. Expression of monocyte chemoattractant protein-1 in the lesional skin of systemic sclerosis. J Dermatol Sci 2001;26(2):133-9
67. Yamamoto T, Takagawa S, Katayama I, et al. Animal model of sclerotic skin. I: local injections of bleomycin induce sclerotic skin mimicking scleroderma. J Invest Dermatol 1999;112(4):456-62
68. Yamamoto T, Takahashi Y, Takagawa S, et al. Animal model of sclerotic skin. II. Bleomycin induced scleroderma in genetically mast cell deficient WBB6F1-W/W(V) mice. J Rheumatol 1999;26(12):2628-34
69. Yamamoto T, Nishioka K. Role of monocyte chemoattractant protein-1 and its receptor, CCR-2, in the pathogenesis of bleomycin-induced scleroderma. J Invest Dermatol 2003;121(3):510-6
70. Carulli MT, Ong VH, Ponticos M, et al. Chemokine receptor CCR2 expression by systemic sclerosis fibroblasts: evidence for autocrine regulation of myofibroblast differentiation. Arthritis Rheum 2005;52(12):3772-82
71. Kumar V, Cotran RS, Robbins SL, editors. Robbins basic pathology. 7th edition. Philadelphia, Pennsylvania, USA: Saunders; 2003
72. Manson JJ, Rahman A. Systemic lupus erythematosus. Orphanet J Rare Dis 2006;1:6
73. Hasegawa H, Kohno M, Sasaki M, et al. Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice. Arthritis Rheum 2003;48(9):2555-66
74. Wada T, Yokoyama H, Su SB, et al. Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis. Kidney Int 1996;49(3):761-7
75. Noris M, Bernasconi S, Casiraghi F, et al. Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis. Lab Invest 1995;73(6):804-9
76. Pérez de Lema G, Maier H, Franz TJ, Escribese M. Chemokine receptor Ccr2 defi ciency reduces renal disease and prolongs survival in MRL/lpr lupus-prone mice. J Am Soc Nephrol 2005;16(12):3592-601
77. Kulkarni O, Pawar RD, Purschke W, Eulberg D. Spiegelmer inhibition of CCL2/MCP-1 ameliorates lupus nephritis in MRL-(Fas)lpr mice. J Am Soc Nephrol 2007;18(8):2350-8
78. Kulkarni O, Anders HJ. CCL2/MCP-1 als neues target beim systemischem lupus erythematodes und der lupusnephritis. Z Rheumatol 2008;67(3):220-4
79. Nilsson J, Hansson GK. Autoimmunity in atherosclerosis: a protective response losing control? J Intern Med 2008;263:464-78
80. Pereira IA, Borba EF. Multiple factors determine the increased prevalence of atherosclerosis in rheumatoid arthritis. Acta Reumatol Port 2008;33(1):47-55
81. Pertovaara M, Raitala A, Juonala M, et al. Autoimmunity and atherosclerosis: functional polymorphism of PTPN22 is associated with phenotypes related to the risk of atherosclerosis. The Cardiovascular Risk in Young Finns Study. Clin Exp Immunol 2007;147(2):265-9
82. Takeya M, Yoshimura T, Leonard EJ, Takahashi K. Detection of monocyte chemoattractant protein-1 in human atherosclerotic lesions by an antimonocyte chemoattractant protein-1 monoclonal antibody. Hum Pathol 1993;24:534-9
83. Ylä-Herttuala S, Lipton BA, Rosenfeld ME, et al. Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. Proc Natl Acad Sci USA 1991;88:5252-6
84. Gu L, Okada Y, Clinton SK, et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptordeficient mice. Mol Cell 1998;2:275-81
85. Boring L, Gosling J, Cleary M, Charo IF. Decreased lesion formation in CCR2-/-mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998;394:894-7
86. Schepers A, Eefting D, Bonta PI, et al. Anti-MCP-1 gene therapy inhibits vascular smooth muscle cells proliferation and attenuates vein graft thickening both in vitro and in vivo. Arterioscler Thromb Vasc Biol 2006;26:2063-9
87. Millennium announces MLN1202 significantly reduced marker of systemic inflammation and identifies genomic biomarker for responders. Millennium Pharmaceuticals, Inc., 2007. Available from: http://investor.millennium.com/