Recent clinical trends in Toll-like receptor targeting therapeutics.
Toll-like receptor
adjuvant
clinical trial
drug
innate immunity
Journal
Medicinal research reviews
ISSN: 1098-1128
Titre abrégé: Med Res Rev
Pays: United States
ID NLM: 8103150
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
16
06
2018
revised:
18
10
2018
accepted:
21
10
2018
pubmed:
20
11
2018
medline:
3
8
2019
entrez:
20
11
2018
Statut:
ppublish
Résumé
Toll-like receptors (TLRs) are germline-encoded receptors that are central to innate and adaptive immune responses. Owing to their vital role in inflammation, TLRs are rational targets in clinics; thus, many ligands and biologics have been reported to overcome the progression of various inflammatory and malignant conditions and support the immune system. For each TLR, at least one, and often many, drug formulations are being evaluated. Ligands reported as stand-alone drugs may also be reported based on their use in combinatorial therapeutics as adjuvants. Despite their profound efficacy in TLR-modulation in preclinical studies, multiple drugs have been terminated at different stages of clinical trials. Here, TLR modulating drugs that have been evaluated in clinical trials are discussed, along with their mode of action, suggestive failure reasons, and ways to improve the clinical outcomes. This review presents recent advances in TLR-targeting drugs and provides directions for more successful immune system manipulation.
Identifiants
pubmed: 30450666
doi: 10.1002/med.21553
pmc: PMC6587958
doi:
Substances chimiques
Adjuvants, Immunologic
0
Ligands
0
Toll-Like Receptors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Pagination
1053-1090Informations de copyright
© 2018 The Authors. Medicinal Research Reviews Published by Wiley Periodicals, Inc.
Références
Immunity. 2016 Oct 18;45(4):737-748
pubmed: 27742543
Immunology. 2012 Aug;136(4):370-9
pubmed: 22444240
Arthritis Rheum. 2000 Oct;43(10):2160-8
pubmed: 11037875
Oncogene. 2014 Jul 3;33(27):3485-95
pubmed: 23934186
Oncologist. 2008 Aug;13(8):859-75
pubmed: 18701762
Allergy. 2014 Dec;69(12):1602-9
pubmed: 25093709
Inflamm Bowel Dis. 2011 Jul;17(7):1464-73
pubmed: 21674704
J Autoimmun. 2010 Jun;34(4):339-48
pubmed: 19944565
NCHS Data Brief. 2011 Jun;(62):1-8
pubmed: 22142805
Infect Immun. 2015 Apr;83(4):1641-9
pubmed: 25667264
Cancer Treat Rev. 2016 Nov;50:35-47
pubmed: 27612280
Science. 2004 Mar 5;303(5663):1522-6
pubmed: 15001781
Invest New Drugs. 2014 Dec;32(6):1278-84
pubmed: 24894651
J Immunol. 2009 Dec 1;183(11):7461-70
pubmed: 19917698
Curr Opin Immunol. 2012 Jun;24(3):310-5
pubmed: 22521140
Crit Care Med. 1998 Dec;26(12):2078-86
pubmed: 9875924
Cancer Res. 2008 Jan 15;68(2):615-22
pubmed: 18199559
Genes Dev. 1999 Apr 15;13(8):1015-24
pubmed: 10215628
Genes Dev. 2005 Nov 15;19(22):2668-81
pubmed: 16260493
Trends Mol Med. 2007 Nov;13(11):460-9
pubmed: 18029230
Cell. 2007 Sep 21;130(6):1071-82
pubmed: 17889651
Springer Semin Immunopathol. 2006 Oct;28(2):131-43
pubmed: 17047954
Genes Dev. 2012 Feb 1;26(3):203-34
pubmed: 22302935
PLoS One. 2015 Jul 28;10(7):e0132921
pubmed: 26218271
Med Res Rev. 2019 May;39(3):1053-1090
pubmed: 30450666
J Med Chem. 2016 Mar 10;59(5):1711-26
pubmed: 26861551
Mol Cell. 2003 Feb;11(2):293-302
pubmed: 12620219
Nat Rev Rheumatol. 2016 Jun;12(6):344-57
pubmed: 27170508
Cell Immunol. 2011;267(1):9-16
pubmed: 21092943
Inflamm Bowel Dis. 2009 Jul;15(7):997-1006
pubmed: 19229991
Cell. 2007 Sep 7;130(5):906-17
pubmed: 17803912
Pediatr Int. 2006 Aug;48(4):403-5
pubmed: 16911087
Sci Rep. 2017 Jan 20;7:40878
pubmed: 28106112
Clin Cancer Res. 2012 Jan 15;18(2):499-509
pubmed: 22128302
Immunobiology. 2008;213(3-4):205-24
pubmed: 18406368
Biomaterials. 2017 May;126:49-60
pubmed: 28254693
Annu Rev Immunol. 2003;21:335-76
pubmed: 12524386
Hum Vaccin Immunother. 2016 Mar 3;12(3):612-22
pubmed: 26513200
J Biol Chem. 2014 Dec 19;289(51):35237-45
pubmed: 25391648
Vaccine. 2013 Jul 18;31(33):3327-32
pubmed: 23735678
Vaccine. 2011 Apr 12;29(17):3341-55
pubmed: 20713100
Mol Cell. 2011 Nov 18;44(4):559-71
pubmed: 22099304
J Hepatol. 2018 Mar;68(3):431-440
pubmed: 29104121
Science. 2005 Jul 22;309(5734):581-5
pubmed: 15961631
Oncogene. 2018 Jan 25;37(4):439-449
pubmed: 28967901
Nat Immunol. 2001 Aug;2(8):675-80
pubmed: 11477402
Infect Immun. 2008 May;76(5):2123-9
pubmed: 18332208
Structure. 2011 Apr 13;19(4):447-59
pubmed: 21481769
Science. 2004 Mar 5;303(5663):1526-9
pubmed: 14976262
Am J Physiol Heart Circ Physiol. 2014 Jan 15;306(2):H184-96
pubmed: 24163075
J Biol Chem. 2006 Apr 7;281(14):9049-57
pubmed: 16455646
Ann Rheum Dis. 2004 Nov;63 Suppl 2:ii90-ii91
pubmed: 15479881
J Immunol. 2010 Nov 15;185(10):5677-82
pubmed: 21048152
Nat Struct Mol Biol. 2015 Feb;22(2):109-15
pubmed: 25599397
Cell Host Microbe. 2013 Aug 14;14(2):148-58
pubmed: 23954154
J Immunol. 2007 Mar 1;178(5):2655-60
pubmed: 17312106
Circ Cardiovasc Interv. 2012 Apr;5(2):279-87
pubmed: 22354933
PLoS One. 2012;7(7):e41144
pubmed: 22829921
Oncotarget. 2016 Jan 19;7(3):2936-50
pubmed: 26655090
Nat Rev Immunol. 2014 Feb;14(2):109-21
pubmed: 24457485
Nature. 2009 Apr 30;458(7242):1191-5
pubmed: 19252480
Front Physiol. 2017 Jul 19;8:508
pubmed: 28769820
Nat Immunol. 2006 Jun;7(6):598-605
pubmed: 16699525
Annu Rev Immunol. 2011;29:447-91
pubmed: 21219179
JAMA. 2013 Mar 20;309(11):1154-62
pubmed: 23512062
Cytokine. 2008 May;42(2):145-151
pubmed: 18304834
Cell Mol Immunol. 2018 May;15(5):428-437
pubmed: 29553135
Atherosclerosis. 2010 Dec;213(2):429-35
pubmed: 20843518
J Immunol. 2011 Apr 15;186(8):4794-804
pubmed: 21398612
JAMA Intern Med. 2016 Dec 1;176(12):1826-1833
pubmed: 27723879
Vaccine. 2011 Jul 12;29(31):4897-902
pubmed: 21596084
J Immunol. 2005 Feb 1;174(3):1259-68
pubmed: 15661881
F1000Res. 2016 Nov 3;5:2629
pubmed: 28105310
Nat Immunol. 2010 May;11(5):373-84
pubmed: 20404851
J Virol. 2013 Mar;87(6):3261-70
pubmed: 23302870
Cytokine. 2008 Mar;41(3):254-62
pubmed: 18221884
J Exp Med. 2005 Oct 17;202(8):1131-9
pubmed: 16230478
Acta Dermatovenerol Croat. 2017 Jul;25(2):164-166
pubmed: 28871935
Science. 2007 Dec 7;318(5856):1628-32
pubmed: 17991829
Oncotarget. 2015 Oct 20;6(32):33781-90
pubmed: 26418952
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3012-7
pubmed: 26929371
J Immunol. 2010 Feb 15;184(4):1840-8
pubmed: 20089701
Nat Rev Drug Discov. 2016 Jun 30;15(7):447
pubmed: 27357012
Clin Exp Immunol. 2007 Mar;147(3):497-503
pubmed: 17302899
Clin Pharmacol Ther. 2017 Feb;101(2):200-208
pubmed: 27706798
Clin Dev Immunol. 2012;2012:836485
pubmed: 22737174
Nat Chem Biol. 2018 Jan;14(1):58-64
pubmed: 29155428
Front Physiol. 2011 Jul 27;2:41
pubmed: 21845181
Nature. 2015 Apr 30;520(7549):702-5
pubmed: 25686612
Exp Mol Med. 2013 Feb 22;45:e11
pubmed: 23429360
Immunology. 2014 Oct;143(2):258-68
pubmed: 24766519
Nature. 2010 Jun 17;465(7300):885-90
pubmed: 20485341
Lancet Infect Dis. 2014 May;14(5):372-3
pubmed: 24758995
Infect Immun. 2007 Feb;75(2):545-52
pubmed: 17118981
Nat Immunol. 2008 Apr;9(4):361-8
pubmed: 18297073
Infect Immun. 2009 Jul;77(7):2925-31
pubmed: 19433546
Immunity. 2011 May 27;34(5):637-50
pubmed: 21616434
Immunopharmacol Immunotoxicol. 2014 Aug;36(4):251-60
pubmed: 24555494
Nature. 2001 Jul 19;412(6844):346-51
pubmed: 11460167
Adv Drug Deliv Rev. 2008 Apr 29;60(7):805-12
pubmed: 18262679
Immunity. 2006 Sep;25(3):417-28
pubmed: 16973389
J Allergy Clin Immunol. 2018 Apr;141(4):1220-1230
pubmed: 28734844
Cancer Genet. 2011 Feb;204(2):77-83
pubmed: 21494579
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12487-92
pubmed: 16891416
Biochim Biophys Acta. 2001 Mar 19;1518(1-2):157-61
pubmed: 11267672
Int Immunopharmacol. 2018 Jun;59:391-412
pubmed: 29730580
N Engl J Med. 2017 Sep 7;377(10):911-922
pubmed: 28877023
Immunity. 2016 Oct 18;45(4):705-707
pubmed: 27760331
Crit Rev Biochem Mol Biol. 2015;50(5):359-79
pubmed: 25857820
Trials. 2017 Mar 14;18(1):122
pubmed: 28288676
PLoS One. 2014 Jun 24;9(6):e100543
pubmed: 24959742
Immunity. 2009 Dec 18;31(6):873-84
pubmed: 19931471
Cell Signal. 2014 Nov;26(11):2350-7
pubmed: 25093807
Cell. 2006 Feb 24;124(4):783-801
pubmed: 16497588
Clin Pharmacol Ther. 2013 Nov;94(5):593-600
pubmed: 23880971
J Exp Med. 2012 Aug 27;209(9):1689-702
pubmed: 22908325
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5598-603
pubmed: 15034168
F1000Res. 2017 Feb 7;6:113
pubmed: 28232867
BMC Biol. 2010 May 21;8:61
pubmed: 20529239
Nat Immunol. 2008 Apr;9(4):369-77
pubmed: 18345001
Arthritis Rheum. 2000 Mar;43(3):593-8
pubmed: 10728753
Curr Med Chem. 2016;23(33):3754-3774
pubmed: 27604089
Infect Immun. 2011 Sep;79(9):3576-87
pubmed: 21646453
N Engl J Med. 1972 Sep 14;287(11):553-5
pubmed: 5050429
Nat Immunol. 2009 Jun;10(6):579-86
pubmed: 19412184
PLoS One. 2015 Jul 06;10(7):e0132336
pubmed: 26147469
Nature. 2002 Dec 19-26;420(6917):860-7
pubmed: 12490959
Curr Genomics. 2012 Dec;13(8):633-45
pubmed: 23730203
J Am Chem Soc. 2011 Mar 23;133(11):3764-7
pubmed: 21355588
J Leukoc Biol. 2009 Apr;85(4):664-72
pubmed: 19164128
Biochem Pharmacol. 2009 Oct 1;78(7):863-72
pubmed: 19576181
Int Rev Immunol. 2014 Nov-Dec;33(6):443-53
pubmed: 24911430
Nat Immunol. 2010 Aug;11(8):734-42
pubmed: 20639876
Science. 2008 Apr 18;320(5874):379-81
pubmed: 18420935
J Leukoc Biol. 2001 Mar;69(3):474-81
pubmed: 11261796
Front Immunol. 2014 Nov 28;5:614
pubmed: 25506346
Innate Immun. 2013;19(2):184-92
pubmed: 23035017
Radiat Res. 2017 May;187(5):570-580
pubmed: 28323577
Expert Rev Anti Infect Ther. 2012 Jun;10(6):701-6
pubmed: 22734959
BMC Cancer. 2016 Jul 07;16:422
pubmed: 27389279
Cancer Cell. 2012 Apr 17;21(4):504-16
pubmed: 22516259
Science. 2007 Jun 15;316(5831):1632-4
pubmed: 17569869
Nat Rev Immunol. 2011 Nov 18;11(12):807-22
pubmed: 22094985
Science. 2013 Mar 22;339(6126):1426-9
pubmed: 23520111
Clin Exp Allergy. 2017 Sep;47(9):1193-1203
pubmed: 28681506
F1000Prime Rep. 2014 Nov 04;6:97
pubmed: 25580251
J Med Chem. 2017 Jun 22;60(12):5029-5044
pubmed: 28537730
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4478-84
pubmed: 25288745
Nat Immunol. 2011 Jul 03;12(8):742-51
pubmed: 21725320
Int J Chron Obstruct Pulmon Dis. 2016 Sep 29;11:2409-2417
pubmed: 27729782
J Immunol. 2011 Apr 15;186(8):4819-27
pubmed: 21402890
Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13994-9
pubmed: 26508631
J Immunol. 2000 Dec 15;165(12):7096-101
pubmed: 11120839
J Virol. 2005 Nov;79(22):14355-70
pubmed: 16254370
Cell Microbiol. 2007 May;9(5):1087-98
pubmed: 17359235
Scand J Immunol. 2015 Dec;82(6):523-31
pubmed: 26332048
Front Immunol. 2013 Nov 18;4:387
pubmed: 24302927
Clin Cancer Res. 2017 Apr 15;23(8):1955-1966
pubmed: 27702821
Front Immunol. 2018 Mar 14;9:457
pubmed: 29593720
Cell. 2000 Oct 13;103(2):351-61
pubmed: 11057907
Immunotargets Ther. 2016 Aug 22;5:69-80
pubmed: 27579291
J Immunol. 2008 Jun 1;180(11):7764-73
pubmed: 18490781
Curr Mol Med. 2002 Sep;2(6):545-56
pubmed: 12243247
FEBS J. 2013 Dec;280(23):6196-212
pubmed: 24090058
Pulm Pharmacol Ther. 2015 Jun;32:93-100
pubmed: 25722071
Allergy. 2015 Sep;70(9):1160-8
pubmed: 26042362
Clin Pharmacol Ther. 2018 Aug;104(2):335-345
pubmed: 29134633
Sci Rep. 2015 Dec 15;5:18239
pubmed: 26667391
Eur Respir J. 2017 May 23;49(5):
pubmed: 28536254
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E884-93
pubmed: 26831104