Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications.
4-1BB (CD137)
TNFR
agonist
autoimmunity
cancer immunotherapy
clinical trials
vaccination
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
24
05
2023
accepted:
03
08
2023
medline:
5
9
2023
pubmed:
4
9
2023
entrez:
4
9
2023
Statut:
epublish
Résumé
Costimulatory receptors on immune cells represent attractive targets for immunotherapy given that these molecules can increase the frequency of individual protective immune cell populations and their longevity, as well as enhance various effector functions. 4-1BB, a member of the TNF receptor superfamily, also known as CD137 and TNFRSF9, is one such molecule that is inducible on several cell types, including T cells and NK cells. Preclinical studies in animal models have validated the notion that stimulating 4-1BB with agonist reagents or its natural ligand could be useful to augment conventional T cell and NK cell immunity to protect against tumor growth and against viral infection. Additionally, stimulating 4-1BB can enhance regulatory T cell function and might be useful in the right context for suppressing autoimmunity. Two human agonist antibodies to 4-1BB have been produced and tested in clinical trials for cancer, with variable results, leading to the production of a wealth of second-generation antibody constructs, including bi- and multi-specifics, with the hope of optimizing activity and selectivity. Here, we review the progress to date in agonism of 4-1BB, discuss the complications in targeting the immune system appropriately to elicit the desired activity, together with challenges in engineering agonists, and highlight the untapped potential of manipulating this molecule in infectious disease and autoimmunity.
Identifiants
pubmed: 37662949
doi: 10.3389/fimmu.2023.1228486
pmc: PMC10469789
doi:
Substances chimiques
Antibodies
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1228486Informations de copyright
Copyright © 2023 Salek-Ardakani, Zajonc and Croft.
Déclaration de conflit d'intérêts
SS-A is employed by Yz Consulting. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Oncoimmunology. 2015 Jan 09;4(3):e970918
pubmed: 25949891
Semin Oncol. 2010 Oct;37(5):508-16
pubmed: 21074066
J Clin Invest. 2021 Dec 1;131(23):
pubmed: 34673568
J Immunol. 2002 May 1;168(9):4262-7
pubmed: 11970964
J Virol. 2018 Jan 2;92(2):
pubmed: 29093082
J Immunol. 2010 Jan 1;184(1):512-20
pubmed: 19949082
Int Immunol. 2006 Feb;18(2):325-33
pubmed: 16373363
Circulation. 2008 Mar 11;117(10):1292-301
pubmed: 18285570
Int J Mol Sci. 2021 May 26;22(11):
pubmed: 34073188
Nat Med. 2004 Oct;10(10):1088-94
pubmed: 15448685
Cancer Discov. 2022 May 2;12(5):1248-1265
pubmed: 35176764
J Immunol. 2009 Aug 1;183(3):1851-61
pubmed: 19596991
MAbs. 2023 Jan-Dec;15(1):2167189
pubmed: 36727218
Clin Dev Immunol. 2012;2012:439235
pubmed: 22312406
Vaccine. 2006 Nov 17;24(47-48):6867-74
pubmed: 17050052
Clin Exp Immunol. 1996 Dec;106(3):427-33
pubmed: 8973608
Vaccine. 2012 Jan 17;30(4):691-702
pubmed: 22146759
J Biol Chem. 2018 Jun 29;293(26):9958-9969
pubmed: 29720398
FASEB J. 2007 Feb;21(2):456-63
pubmed: 17167064
Immunol Res. 2004;29(1-3):197-208
pubmed: 15181282
Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12669-74
pubmed: 21768335
EBioMedicine. 2020 Feb;52:102647
pubmed: 32028068
Mucosal Immunol. 2017 Sep;10(5):1294-1309
pubmed: 28051085
Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165605
pubmed: 31740402
Crit Rev Immunol. 2019;39(6):409-421
pubmed: 32421955
J Clin Invest. 2004 Apr;113(8):1218-24
pubmed: 15085201
Front Pharmacol. 2022 Jul 05;13:924197
pubmed: 35865955
JCI Insight. 2020 Mar 12;5(5):
pubmed: 32161196
Cancer Res. 2011 Feb 1;71(3):801-11
pubmed: 21266358
Trends Mol Med. 2023 Jan;29(1):48-60
pubmed: 36344331
Nat Commun. 2019 May 20;10(1):2141
pubmed: 31105267
J Immunol. 2007 Apr 1;178(7):4194-213
pubmed: 17371976
Circ J. 2017 Nov 24;81(12):1945-1952
pubmed: 28747613
Adv Exp Med Biol. 2009;647:120-9
pubmed: 19760070
Vaccine. 2005 May 20;23(27):3493-9
pubmed: 15855007
Autoimmun Rev. 2004 Nov;3(7-8):524-9
pubmed: 15546801
J Immunother Cancer. 2021 Jul;9(7):
pubmed: 34230109
Mol Cancer. 2023 Jun 13;22(1):94
pubmed: 37312116
PLoS One. 2014 Aug 20;9(8):e105520
pubmed: 25140889
J Immunol. 2019 Apr 15;202(8):2482-2492
pubmed: 30867239
Clin Cancer Res. 2022 Aug 2;28(15):3387-3399
pubmed: 35121624
J Immunol. 2005 Jun 15;174(12):7625-32
pubmed: 15944263
Nat Commun. 2021 Nov 4;12(1):6360
pubmed: 34737267
Blood. 2008 Oct 1;112(7):2847-57
pubmed: 18645038
Nat Med. 2002 Dec;8(12):1405-13
pubmed: 12426559
Cell Rep. 2018 Oct 23;25(4):909-920.e4
pubmed: 30355497
J Immunol. 2004 Jan 15;172(2):981-8
pubmed: 14707071
Drug Res (Stuttg). 2016 Apr;66(4):211-6
pubmed: 26418415
Front Immunol. 2022 Aug 02;13:897991
pubmed: 35983060
Clin Cancer Res. 2017 Apr 15;23(8):1929-1936
pubmed: 27756788
Biol Blood Marrow Transplant. 2009 Mar;15(3):306-14
pubmed: 19203721
Cell Mol Immunol. 2015 Jul;12(4):456-65
pubmed: 25195511
Front Immunol. 2012 Nov 08;3:332
pubmed: 23162550
J Immunol. 2002 Nov 1;169(9):5005-9
pubmed: 12391215
Eur J Immunol. 2009 Jun;39(6):1552-63
pubmed: 19499519
J Immunol. 2000 Mar 1;164(5):2320-5
pubmed: 10679066
Oncoimmunology. 2013 Nov 1;2(11):e26859
pubmed: 24482752
Immune Netw. 2010 Jun;10(3):104-8
pubmed: 20631881
iScience. 2022 Aug 17;25(9):104958
pubmed: 36072551
Curr Top Microbiol Immunol. 2014;382:321-52
pubmed: 25116107
J Clin Invest. 2003 May;111(10):1505-18
pubmed: 12750400
Scand J Immunol. 2007 Oct;66(4):435-40
pubmed: 17850588
J Clin Invest. 2014 May;124(5):2246-59
pubmed: 24667641
J Immunol. 2005 Oct 15;175(8):4897-903
pubmed: 16210591
Clin Cancer Res. 2021 Jun 1;27(11):3167-3177
pubmed: 33785484
Blood. 2018 Jan 4;131(1):49-57
pubmed: 29118009
J Immunol. 2013 May 1;190(9):4627-39
pubmed: 23536631
PLoS One. 2011;6(9):e24250
pubmed: 21935390
Nat Rev Clin Oncol. 2020 Jul;17(7):418-434
pubmed: 32242094
PLoS One. 2011 Apr 29;6(4):e19499
pubmed: 21559358
J Immunol. 2008 Apr 15;180(8):5267-74
pubmed: 18390707
Endocrinology. 2010 Oct;151(10):4725-35
pubmed: 20719857
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5348-53
pubmed: 12695569
Cell Mol Immunol. 2008 Feb;5(1):47-53
pubmed: 18318994
Clin Cancer Res. 2017 Sep 15;23(18):5349-5357
pubmed: 28634283
Nat Commun. 2018 Jan 2;9(1):6
pubmed: 29295974
J Clin Invest. 2006 Apr;116(4):1025-36
pubmed: 16528411
Cancer Res. 2006 Jul 15;66(14):7276-84
pubmed: 16849577
Immunology. 2004 Sep;113(1):89-98
pubmed: 15312139
Nat Commun. 2018 Nov 8;9(1):4679
pubmed: 30410017
Vaccine. 2010 Feb 3;28(5):1300-9
pubmed: 19944789
Nat Immunol. 2002 Jun;3(6):536-41
pubmed: 12021777
Immunol Rev. 2009 May;229(1):192-215
pubmed: 19426223
Sci Transl Med. 2023 May 10;15(695):eabp9229
pubmed: 37163618
J Exp Med. 2014 Jun 30;211(7):1433-48
pubmed: 24958847
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1291-6
pubmed: 14745033
J Immunother. 2015 Feb-Mar;38(2):62-70
pubmed: 25658615
Clin Cancer Res. 2020 Jun 1;26(11):2524-2534
pubmed: 32144134
J Am Heart Assoc. 2017 Mar 13;6(3):
pubmed: 28288971
Cancer Discov. 2021 Jan;11(1):158-175
pubmed: 32847940
Trends Pharmacol Sci. 2008 Aug;29(8):383-90
pubmed: 18599129
Nat Rev Immunol. 2003 Aug;3(8):609-20
pubmed: 12974476
Cancer Cell. 2018 Apr 9;33(4):664-675.e4
pubmed: 29576376
Blood. 2008 Aug 1;112(3):699-707
pubmed: 18519814
Am J Hematol. 2020 May;95(5):510-520
pubmed: 32052473
Blood. 2007 Jul 15;110(2):776-82
pubmed: 17363737
Front Immunol. 2018 Nov 15;9:2618
pubmed: 30524423
Cancer Discov. 2023 Mar 1;13(3):552-569
pubmed: 36576322
Clin Cancer Res. 2022 Aug 2;28(15):3182-3184
pubmed: 35648093
Int Arch Allergy Immunol. 2009;148(4):305-10
pubmed: 19001790
Front Immunol. 2022 Sep 29;13:970290
pubmed: 36248847
Mol Cancer Ther. 2014 Jan;13(1):112-21
pubmed: 24198185
Blood. 2007 Dec 15;110(13):4360-6
pubmed: 17878400
Mol Cancer Ther. 2020 Apr;19(4):1040-1051
pubmed: 31974274
Autoimmun Rev. 2013 Jan;12(3):436-43
pubmed: 22944299
Clin Cancer Res. 2018 Apr 15;24(8):1816-1823
pubmed: 29549159
Nat Commun. 2018 Nov 15;9(1):4809
pubmed: 30442944
Transl Oncol. 2022 Jul 9;23:101481
pubmed: 35820360
J Biol Chem. 2019 Feb 8;294(6):1831-1845
pubmed: 30545939
Antibodies (Basel). 2020 Nov 17;9(4):
pubmed: 33212886
J Biol Chem. 2018 Jun 22;293(25):9880-9891
pubmed: 29720399
J Immunol. 2009 Jun 1;182(11):6753-62
pubmed: 19454670
J Immunol. 2005 Nov 15;175(10):6378-89
pubmed: 16272290
Sci Transl Med. 2019 Jun 12;11(496):
pubmed: 31189721
J Immunol. 2002 Feb 1;168(3):1457-65
pubmed: 11801689
J Immunol. 2006 Jul 15;177(2):814-21
pubmed: 16818735
J Virol. 2019 Nov 26;93(24):
pubmed: 31578287
J Immunol. 2012 Sep 15;189(6):2697-701
pubmed: 22896640
J Autoimmun. 2023 Jan 11;:102986
pubmed: 36639301
Eur J Immunol. 1998 Mar;28(3):1116-21
pubmed: 9541607
Nat Med. 1997 Jun;3(6):682-5
pubmed: 9176498
PLoS One. 2013 Dec 19;8(12):e84927
pubmed: 24367702
J Immunol. 2014 Jan 1;192(1):293-9
pubmed: 24285837
Blood. 2008 Oct 15;112(8):3303-11
pubmed: 18660382
Clin Cancer Res. 2020 Aug 1;26(15):4154-4167
pubmed: 32345647
Sci Rep. 2020 Jan 20;10(1):643
pubmed: 31959763
J Immunother Cancer. 2022 Jun;10(6):
pubmed: 35688554
Cytokine. 2006 Jun;34(5-6):233-42
pubmed: 16899371
Cell Rep. 2020 Mar 24;30(12):4124-4136.e5
pubmed: 32209473
Cancer Immunol Immunother. 2010 Aug;59(8):1223-33
pubmed: 20336294
Ann N Y Acad Sci. 2003 Apr;987:230-5
pubmed: 12727643
J Immunol. 2010 Dec 15;185(12):7654-62
pubmed: 21059892
Nat Commun. 2021 Dec 15;12(1):7296
pubmed: 34911975
Invest Ophthalmol Vis Sci. 2005 Feb;46(2):596-603
pubmed: 15671287
Immunol Lett. 2016 Oct;178:131-9
pubmed: 27592361
Diabetes. 2007 Jan;56(1):186-96
pubmed: 17192481
J Immunol. 2006 Mar 1;176(5):2739-48
pubmed: 16493029
J Immunol. 1999 Apr 15;162(8):5003-10
pubmed: 10202049
Clin Cancer Res. 2018 Mar 1;24(5):1138-1151
pubmed: 29301830
Protein Cell. 2018 Jan;9(1):63-73
pubmed: 28986820
Cancer Lett. 2013 Apr 28;330(2):190-9
pubmed: 23219755
Proc Natl Acad Sci U S A. 2021 Jun 29;118(26):
pubmed: 34172583
Cancer Sci. 2020 Jun;111(6):1943-1957
pubmed: 32304268
Nat Commun. 2021 Jul 21;12(1):4445
pubmed: 34290245
Clin Cancer Res. 2014 Jan 1;20(1):44-55
pubmed: 24045181
Cancer Immunol Immunother. 2012 Oct;61(10):1721-33
pubmed: 22406983
Vaccine. 2011 Aug 26;29(37):6301-12
pubmed: 21704101
Proc Natl Acad Sci U S A. 1989 Mar;86(6):1963-7
pubmed: 2784565
Immunol Lett. 2005 Nov 15;101(2):210-6
pubmed: 16026855
Clin Cancer Res. 2019 Oct 1;25(19):5878-5889
pubmed: 31138587
Cancer Immunol Res. 2020 Jun;8(6):781-793
pubmed: 32273279
Int J Hematol. 2006 Jan;83(1):23-8
pubmed: 16443548
Nano Lett. 2023 May 24;23(10):4191-4200
pubmed: 37186944
Immunol Today. 1993 May;14(5):215-21
pubmed: 8517920
J Transl Med. 2022 Oct 12;20(1):467
pubmed: 36224560
Hepatology. 2020 Mar;71(3):955-971
pubmed: 31353502
Adv Immunol. 2018;140:1-20
pubmed: 30366517
J Clin Invest. 2020 Mar 2;130(3):1405-1416
pubmed: 32015231
J Biol Chem. 2005 Dec 16;280(50):41472-81
pubmed: 16204238
J Immunol. 2011 Aug 15;187(4):1634-42
pubmed: 21742975
J Immunol. 2004 Aug 15;173(4):2428-34
pubmed: 15294956
Oncoimmunology. 2012 Jul 1;1(4):419-431
pubmed: 22754760
Cell Immunol. 2005 Dec;238(2):76-86
pubmed: 16524567
Cancer Res. 2014 Nov 15;74(22):6441-51
pubmed: 25252915
J Med Chem. 2022 Jul 28;65(14):9858-9872
pubmed: 35819182
Cell Mol Immunol. 2021 Aug;18(8):1956-1968
pubmed: 32868911
J Immunol. 2007 Dec 1;179(11):7295-304
pubmed: 18025172
Cell Immunol. 1989 Jul;121(2):414-22
pubmed: 2500256