Targeting CD137 (4-1BB) towards improved safety and efficacy for cancer immunotherapy.
CD137/4-1BB
FcγR mediated cross-linking
TNFR agonist
cancer immunotherapy
conditional activation
costimulatory receptor
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:
19
04
2023
accepted:
22
05
2023
medline:
20
6
2023
pubmed:
19
6
2023
entrez:
19
6
2023
Statut:
epublish
Résumé
T cells play a critical role in antitumor immunity, where T cell activation is regulated by both inhibitory and costimulatory receptor signaling that fine-tune T cell activity during different stages of T cell immune responses. Currently, cancer immunotherapy by targeting inhibitory receptors such as CTLA-4 and PD-1/L1, and their combination by antagonist antibodies, has been well established. However, developing agonist antibodies that target costimulatory receptors such as CD28 and CD137/4-1BB has faced considerable challenges, including highly publicized adverse events. Intracellular costimulatory domains of CD28 and/or CD137/4-1BB are essential for the clinical benefits of FDA-approved chimeric antigen receptor T cell (CAR-T) therapies. The major challenge is how to decouple efficacy from toxicity by systemic immune activation. This review focuses on anti-CD137 agonist monoclonal antibodies with different IgG isotypes in clinical development. It discusses CD137 biology in the context of anti-CD137 agonist drug discovery, including the binding epitope selected for anti-CD137 agonist antibody in competition or not with CD137 ligand (CD137L), the IgG isotype of antibodies selected with an impact on crosslinking by Fc gamma receptors, and the conditional activation of anti-CD137 antibodies for safe and potent engagement with CD137 in the tumor microenvironment (TME). We discuss and compare the potential mechanisms/effects of different CD137 targeting strategies and agents under development and how rational combinations could enhance antitumor activities without amplifying the toxicity of these agonist antibodies.
Identifiants
pubmed: 37334375
doi: 10.3389/fimmu.2023.1208788
pmc: PMC10272836
doi:
Substances chimiques
CD28 Antigens
0
Antibodies, Monoclonal
0
Immunoglobulin G
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1208788Informations de copyright
Copyright © 2023 Liu and Luo.
Déclaration de conflit d'intérêts
Both authors are employed by Adagene Inc. and have an ownership interest in Adagene.
Références
Cancer Discov. 2022 May 2;12(5):1248-1265
pubmed: 35176764
J Immunother Cancer. 2022 Mar;10(3):
pubmed: 35236742
Cancer Cell. 2018 Apr 9;33(4):649-663.e4
pubmed: 29576375
Clin Cancer Res. 2017 Apr 15;23(8):1929-1936
pubmed: 27756788
PLoS One. 2013 Jul 11;8(7):e69677
pubmed: 23874982
Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):185-90
pubmed: 9874793
Cancer Immunol Immunother. 2013 May;62(5):941-8
pubmed: 23543215
Cancer Discov. 2021 Jan;11(1):158-175
pubmed: 32847940
Nat Commun. 2018 Nov 15;9(1):4809
pubmed: 30442944
Annu Rev Med. 2019 Jan 27;70:409-424
pubmed: 30379596
Trends Cell Biol. 2011 Apr;21(4):228-37
pubmed: 21232958
Nat Rev Drug Discov. 2023 Jun;22(6):442-443
pubmed: 37059846
Front Oncol. 2021 May 28;11:663264
pubmed: 34123821
Nature. 2023 Feb;614(7948):539-547
pubmed: 36725933
Nature. 2020 Sep;585(7823):107-112
pubmed: 32728218
J Exp Clin Cancer Res. 2022 Mar 14;41(1):97
pubmed: 35287686
MAbs. 2023 Jan-Dec;15(1):2167189
pubmed: 36727218
Semin Immunol. 1998 Dec;10(6):481-9
pubmed: 9826581
J Immunol. 2012 Nov 15;189(10):4981-8
pubmed: 23053513
Nat Rev Immunol. 2009 Apr;9(4):271-85
pubmed: 19319144
Sci Transl Med. 2021 Aug 25;13(608):
pubmed: 34433637
Nat Commun. 2019 May 20;10(1):2141
pubmed: 31105267
Eur J Cancer. 2006 Apr;42(6):728-34
pubmed: 16524717
Clin Cancer Res. 2022 Aug 2;28(15):3387-3399
pubmed: 35121624
Cancer Res. 2017 Nov 1;77(21):5989-6000
pubmed: 28923858
Nat Commun. 2021 Nov 4;12(1):6360
pubmed: 34737267
Cell Rep. 2018 Oct 23;25(4):909-920.e4
pubmed: 30355497
Front Oncol. 2015 Jun 08;5:117
pubmed: 26106583
Commun Biol. 2021 Jun 23;4(1):772
pubmed: 34162985
J Immunother Cancer. 2021 Nov;9(11):
pubmed: 34725211
Clin Cancer Res. 2021 Jun 1;27(11):3167-3177
pubmed: 33785484
Blood. 2018 Jan 4;131(1):49-57
pubmed: 29118009
Blood. 1995 Feb 15;85(4):1043-52
pubmed: 7849293
Immunity. 2018 Nov 20;49(5):958-970.e7
pubmed: 30446386
PLoS One. 2014 Jan 21;9(1):e86337
pubmed: 24466035
Nat Commun. 2018 Nov 8;9(1):4679
pubmed: 30410017
Cancer Res. 2006 Jul 15;66(14):7276-84
pubmed: 16849577
Cell. 2016 Nov 3;167(4):1067-1078.e16
pubmed: 27773482
Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):E5290-9
pubmed: 26351680
Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19501-6
pubmed: 24218606
Cancer Discov. 2023 Mar 1;13(3):552-569
pubmed: 36576322
Sci Signal. 2020 Mar 31;13(625):
pubmed: 32234960
Clin Cancer Res. 2019 Oct 1;25(19):5732-5734
pubmed: 31366600
Mol Cancer Ther. 2020 Apr;19(4):1040-1051
pubmed: 31974274
Clin Cancer Res. 2018 Apr 15;24(8):1816-1823
pubmed: 29549159
Nat Med. 2018 Jul;24(7):978-985
pubmed: 29942094
Sci Transl Med. 2019 Jun 12;11(496):
pubmed: 31189721
J Leukoc Biol. 2011 Jan;89(1):21-9
pubmed: 20643812
Nat Med. 1997 Jun;3(6):682-5
pubmed: 9176498
Nat Rev Immunol. 2010 May;10(5):328-43
pubmed: 20414206
Clin Cancer Res. 2020 Aug 1;26(15):4154-4167
pubmed: 32345647
J Immunother Cancer. 2022 Jun;10(6):
pubmed: 35688554
Adv Exp Med Biol. 2007;597:188-201
pubmed: 17633027
Immunity. 2013 Jul 25;39(1):1-10
pubmed: 23890059
Nat Commun. 2021 Jul 21;12(1):4445
pubmed: 34290245
Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):609-618
pubmed: 30587582
Proc Natl Acad Sci U S A. 2021 Jun 29;118(26):
pubmed: 34172583
Clin Cancer Res. 2019 Oct 1;25(19):5878-5889
pubmed: 31138587
Cancer Immunol Res. 2020 Jun;8(6):781-793
pubmed: 32273279
Sci Adv. 2021 Jan 15;7(3):
pubmed: 33523913