Amiselimod (MT-1303), a novel sphingosine 1-phosphate receptor-1 functional antagonist, inhibits progress of chronic colitis induced by transfer of CD4+CD45RBhigh T cells
Autoři:
Kyoko Shimano aff001; Yasuhiro Maeda aff001; Hirotoshi Kataoka aff001; Mikako Murase aff001; Sachiko Mochizuki aff001; Hiroyuki Utsumi aff001; Koichi Oshita aff001; Kunio Sugahara aff001
Působiště autorů:
Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan
aff001
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0226154
Souhrn
Amiselimod (MT-1303) is a novel sphingosine 1-phosphate receptor-1 (S1P1 receptor) modulator with a more favorable cardiac safety profile than other S1P1 receptor modulators. MT-1303 phosphate (MT-1303-P), an active metabolite of MT-1303, exhibits S1P1 receptor agonism at a lower EC50 value than other S1P1 receptor modulators currently being developed. We aimed to evaluate the efficacy of MT-1303 and its mode of action in chronic colitis using an inflammatory bowel disease (IBD) model. Oral administration of MT-1303 (0.3 mg/kg) once daily for 3 days to mice almost completely abolished S1P1 receptor expression on CD4+ T cells from mesenteric lymph nodes, which corresponded to a marked decrease in CD4+ T cell count in peripheral blood, indicating that MT-1303-P acts as a functional antagonist of the S1P1 receptor. The potential benefit of MT-1303 for IBD was assessed using immunodeficient SCID mice with chronic colitis induced by adoptive transfer of CD4+CD45RBhigh T cells from BALB/c mice. An oral dose of 0.1 and 0.3 mg/kg MT-1303 administered daily one week after the cell transfer inhibited the development of chronic colitis with an efficacy comparable to that of an anti-mTNF-α mAb (250 μg/mouse). In addition, MT-1303 administration significantly reduced the number of infiltrating Th1 and Th17 cells into the lamina propria of the colon in colitis mice. Our results suggest that MT-1303 acts as a functional antagonist of the S1P1 receptor on lymphocytes, regulates lymphocyte trafficking, and inhibits infiltration of colitogenic Th1 and Th17 cells into the colon to inhibit the development of chronic colitis.
Klíčová slova:
Body weight – Colitis – Colon – Lymphocytes – Mouse models – T cell receptors – T cells – T helper cells
Zdroje
1. Danese S, Sans M, Flocchi C. Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev. 2004;3(5):394–400. doi: 10.1016/j.autrev.2004.03.002 15288007.
2. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369(9573):1627–40. doi: 10.1016/S0140-6736(07)60750-8 17499605.
3. von Andrian UH, Mackay CR. T-cell function and migration. Two sides of the same coin. N Engl J Med. 2000;343(14):1020–34. doi: 10.1056/NEJM200010053431407 11018170.
4. Pérez-Jeldres T, Tyler CJ, Boyer JD, Karuppuchamy T, Bamias G, Dulai PS, et al. Cell trafficking interference in inflammatory bowel disease: Therapeutic interventions based on basic pathogenesis concepts. Inflamm Bowel Dis. 2019;25(2):270–82. doi: 10.1093/ibd/izy269 30165490.
5. Sugahara K, Maeda Y, Shimano K, Mogami A, Kataoka H, Ogawa K, et al. Amiselimod, a novel sphingosine 1-phosphate receptor-1 modulator, has potent therapeutic efficacy for autoimmune diseases, with low bradycardia risk. Br J Pharmacol. 2017;174(1):15–27. doi: 10.1111/bph.13641 27714763.
6. Harada T, Wilbraham D, de La Borderie G, Inoue S, Bush J, Camm AJ. Cardiac effects of amiselimod compared with fingolimod and placebo: Results of a randomised, parallel-group, phase I study in healthy subjects. Br J Clin Pharmacol. 2017;83 (5):1011–27. doi: 10.1111/bcp.13203 27921320. ClinicalTrials.gov registration number: NCT02193217.
7. Kappos L, Arnold DL, Bar-Or A, Camm J, Derfuss T, Kieseier BC, et al. Safety and efficacy of amiselimod in relapsing multiple sclerosis (MOMENTUM): A randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2016;15(11):1148–59. doi: 10.1016/S1474-4422(16)30192-2 27543447. ClinicalTrials.gov registration number: NCT01742052.
8. Chiba K, Kataoka H, Seki N, Shimano K, Koyama M, Fukunari A, et al. Fingolimod (FTY720), sphingosine 1-phophate receptor modulator, shows superior efficacy as compared with interferon-β in mouse experimental autoimmune encephalomyelitis. Int Immunopharmacol. 2011;11(3):366–72. doi: 10.1016/j.intimp.2010.10.005 20955831.
9. Deguchi Y, Andoh A, Yagi Y, Bamba S, Inatomi O, Tsujikawa T, et al. The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice. Oncol Rep. 2006;16(4):699–703. 16969482.
10. Song J, Matsuda C, Kai Y, Nishida T, Nakajima K, Mizushima T, et al. A novel sphingosine 1-phosphate receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), regulates chronic colitis in interleukin-10 gene-deficient mice. J Pharmacol Exp Ther. 2008;324(1):276–83. doi: 10.1124/jpet.106.119172 17898319.
11. Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, et al. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016;173(11):1778–92. doi: 10.1111/bph.13476 26990079.
12. Sandborn WJ, Feagan BG, Wolf DC, D'Haens G, Vermeire S, Hanauer SB, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med. 2016;374(18):1754–62. doi: 10.1056/NEJMoa1513248 27144850.
13. Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, et al. The selective sphingosine 1‐phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species‐specific effects on heart rate. https://www.ncbi.nlm.nih.gov/pubmed/22646698Br J Pharmacol. 2012;167(5)1035–47. doi: 10.1111/j.1476-5381.2012.02061.x 22646698.
14. Buzard DJ, Kim SH, Lopez L, Kawasaki A, Zhu X, Moody J, et al. Discovery of APD334: Design of a clinical stage functional antagonist of the sphingosine-1-phosphate-1 receptor. ACS Med Chem Lett. 2014;5(12):1313–7. doi: 10.1021/ml500389m 25516790.
15. van Der Lee MM, Bras M, van Koppen CJ, Zaman GJ. beta-Arrestin recruitment assay for the identification of agonists of the sphingosine 1-phosphate receptor EDG1. doi: 10.1177/1087057108326144 sphingosine 1-phosphate receptor EDG1. J Biomol Screen. 2008;13(10):986–998. 19036707.
16. Gisbert JP, Panés J. Loss of response and requirement of infliximab dose intensification in Crohn’s disease: A review. Am J Gastroenterol. 2009;104(3):760–7. doi: 10.1038/ajg.2008.88 19174781.
17. Totsuka T, Kanai T, Uraushihara K, Iiyama R, Yamazaki M, Akiba H, et al. Therapeutic effect of anti-OX40L and anti-TNF-α MAbs in a murine model of chronic colitis. Am J Physiol Gastrointest Liver Physiol. 2003;284(4):G595–G603. doi: 10.1152/ajpgi.00450.2002 12631559.
18. Liu Z, Geboes K, Colpaert S, Overbergh L, Mathieu C, Heremans H, et al. Prevention of experimental colitis in SCID mice reconstituted with CD45RBhigh CD4+ T cells by blocking the CD40-CD154 interactions. J Immunol. 2000;164(11):6005–14. doi: 10.4049/jimmunol.164.11.6005 10820284.
19. Gold R, Comi G, Palace J, Siever A, Gottschalk R, Bijarnia M, et al. Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: A phase 3b, open-label study. J Neurol. 2014:261(2):267–76. doi: 10.1007/s00415-013-7115-8 24221641.
20. Forrest M, Sun SY, Hajdu R, Bergstrom J, Card D, Doherty G, et al. Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther. 2004;309(2):758–68. doi: 10.1124/jpet.103.062828 14747617.
21. Bigaud M, Guerini D, Billich A, Bassilana F, Brinkmann V. Second generation S1P pathway modulators: Research strategies and clinical developments. Biochim Biophys Acta. 2014;1841(5):745–58. doi: 10.1016/j.bbalip.2013.11.001 24239768.
22. Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): A double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263–73. doi: 10.1016/S0140-6736(18)30475-6 29576505.
23. Cohen JA, Arnold DL, Comi G, Bar-Or A, Gujrathi S, Hartung JP, et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): A randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):373–81. doi: 10.1016/S1474-4422(16)00018-1 26879276.
24. Maynard CL, Weaver CT. Intestinal effector T cells in health and disease. Immunity. 2009;31(3):389–400. doi: 10.1016/j.immuni.2009.08.012 19766082.
25. Kiesier P, Fuss IJ, Strober W. Experimental models of inflammatory bowel diseases. Cell Mol Gastroenterol Hepatol. 2015;1(2):154–70. doi: 10.1016/j.jcmgh.2015.01.006 26000334.
26. Mottet C, Uhlig HH, Powrie F. Cure of colitis by CD4+CD25+ regulatory T cells. J Immunol. 2003;170(8):3939–3943. doi: 10.4049/jimmunol.170.8.3939 12682220.
27. Ma C, Huang V, Fedorak DK, Kroeker KI, Dieleman LA, Halloran BP, et al. Crohn’s disease outpatients treated with adalimumab have an earlier secondary loss of response and requirement for dose escalation compared to infliximab: A real life cohort study. J Crohn’s Colitis. 2014;8(11):1454–63. doi: 10.1016/j.crohns.2014.05.007 24947334.
28. Qiu Y, Chen BL, Mao R, Zhang SH, He Y, Zeng ZR, et al. Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn’s disease. J Gastroenterol. 2017;52(5):535–554. doi: 10.1007/s00535-017-1324-3 28275925.
29. D’Haens G, Danese S, Davies M, Watanabe M, Hibi T. Amiselimod, a selective S1P receptor modulator in Crohn’s disease patients: A proof-of-concept study. J Crohn’s Colitis. 2019;13(S1):S055–S056. ClinicalTrials.gov registration number: NCT02378688.
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PLOS One
2019 Číslo 12
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