The antigen-binding moiety in the driver's seat of CARs.
T cell receptor
adoptive T cell therapy
cancer
chimeric antigen receptor
immunotherapy
tumor-infiltrating lymphocyte
Journal
Medicinal research reviews
ISSN: 1098-1128
Titre abrégé: Med Res Rev
Pays: United States
ID NLM: 8103150
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
17
02
2021
received:
10
09
2020
accepted:
21
04
2021
pubmed:
25
5
2021
medline:
5
4
2022
entrez:
24
5
2021
Statut:
ppublish
Résumé
Immuno-oncology has been at the forefront of cancer treatment in recent decades. In particular immune checkpoint and chimeric antigen receptor (CAR)-T cell therapy have achieved spectacular results. Over the years, CAR-T cell development has followed a steady evolutionary path, focusing on increasing T cell potency and sustainability, which has given rise to different CAR generations. However, there was less focus on the mode of interaction between the CAR-T cell and the cancer cell; more specifically on the targeting moiety used in the CAR and its specific properties. Recently, the importance of optimizing this domain has been recognized and the possibilities have been exploited. Over the last 10 years-in addition to the classical scFv-based CARs-single domain CARs, natural receptor-ligand CARs, universal CARs and CARs targeting more than one antigen have emerged. In addition, the specific parameters of the targeting domain and their influence on T cell activation are being examined. In this review, we concisely present the history of CAR-T cell therapy, and then expand on various developments in the CAR ectodomain. We discuss different formats, each with their own advantages and disadvantages, as well as the developments in affinity tuning, avidity effects, epitope location, and influence of the extracellular spacer.
Identifiants
pubmed: 34028069
doi: 10.1002/med.21818
pmc: PMC9292017
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
306-342Informations de copyright
© 2021 The Authors. Medicinal Research Reviews published by Wiley Periodicals LLC.
Références
Int J Hematol. 2012 Apr;95(4):434-44
pubmed: 22407872
Mol Ther Methods Clin Dev. 2018 Dec 31;12:145-156
pubmed: 30666307
J Am Chem Soc. 2020 Apr 8;142(14):6554-6568
pubmed: 32191035
N Engl J Med. 2018 Feb 1;378(5):439-448
pubmed: 29385370
Mol Ther. 2017 Nov 1;25(11):2452-2465
pubmed: 28807568
Clin Cancer Res. 2012 Dec 1;18(23):6436-45
pubmed: 23032741
Gene Ther. 2016 Oct;23(10):718-726
pubmed: 27356950
Nat Med. 2015 Jun;21(6):581-90
pubmed: 25939063
Nat Immunol. 2017 Feb 15;18(3):255-262
pubmed: 28198830
J Immunol. 2004 Dec 15;173(12):7647-53
pubmed: 15585893
Sci Transl Med. 2020 Mar 4;12(533):
pubmed: 32132216
Science. 1999 Jul 30;285(5428):730-2
pubmed: 10426994
Ther Adv Med Oncol. 2020 Mar 09;12:1758835920910347
pubmed: 32215059
J Clin Invest. 2016 Oct 3;126(10):3814-3826
pubmed: 27571406
Cancer Chemother Pharmacol. 2018 Nov;82(5):815-827
pubmed: 30132099
Nat Med. 2007 Dec;13(12):1440-9
pubmed: 18026115
Cancer Res. 2004 Dec 15;64(24):9160-6
pubmed: 15604287
Mol Ther. 2016 Feb;24(2):354-363
pubmed: 26514825
Mol Cancer. 2019 Aug 20;18(1):125
pubmed: 31429760
Pharmacol Ther. 2015 Nov;155:1-10
pubmed: 26213107
Cancer Cell. 2019 Mar 18;35(3):489-503.e8
pubmed: 30889382
N Engl J Med. 1988 Dec 22;319(25):1676-80
pubmed: 3264384
Cancer Immunol Res. 2013 Jul;1(1):26-31
pubmed: 24777247
N Engl J Med. 2016 Dec 29;375(26):2561-9
pubmed: 28029927
Gastroenterology. 2020 Jun;158(8):2250-2265.e20
pubmed: 32060001
Mol Ther Nucleic Acids. 2013 Jul 09;2:e105
pubmed: 23839099
Cancer Immunol Immunother. 2015 Apr;64(4):409-18
pubmed: 25549845
Cancer Immunol Res. 2019 May;7(5):773-783
pubmed: 30842091
Int J Mol Sci. 2018 Jan 30;19(2):
pubmed: 29385713
Cancer Immunol Res. 2013 Jul;1(1):43-53
pubmed: 24409448
Nat Immunol. 2002 Nov;3(11):991-8
pubmed: 12407406
Science. 2006 Sep 29;313(5795):1960-4
pubmed: 17008531
Mol Ther. 2013 Nov;21(11):2087-101
pubmed: 23939024
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Cancer Cell. 2019 Mar 18;35(3):473-488.e6
pubmed: 30889381
J Transl Med. 2015 May 20;13:161
pubmed: 25990251
Cancer Res. 2015 Sep 1;75(17):3505-18
pubmed: 26330164
J Immunol. 2012 Sep 1;189(5):2290-9
pubmed: 22851709
Commun Biol. 2020 Jun 9;3(1):296
pubmed: 32518350
J Biotechnol. 2001 Jun;74(4):277-302
pubmed: 11526908
N Engl J Med. 2014 Oct 16;371(16):1507-17
pubmed: 25317870
Gene Ther. 2015 May;22(5):391-403
pubmed: 25652098
Gene Ther. 2018 Jun;25(3):176-191
pubmed: 29789639
Lancet. 2015 Feb 7;385(9967):517-528
pubmed: 25319501
Hum Gene Ther. 2017 Sep;28(9):726-736
pubmed: 28796529
Mol Ther. 2017 Aug 2;25(8):1933-1945
pubmed: 28479045
Biosens Bioelectron. 2016 Nov 15;85:32-45
pubmed: 27155114
Front Immunol. 2016 Mar 29;7:113
pubmed: 27065074
Mol Ther. 2010 Feb;18(2):413-20
pubmed: 19773745
Curr Opin Immunol. 2009 Apr;21(2):215-23
pubmed: 19327974
J Immunother. 2005 May-Jun;28(3):203-11
pubmed: 15838376
Cancer Res. 2014 Jan 1;74(1):93-103
pubmed: 24197131
Trends Immunol. 2005 Feb;26(2):111-7
pubmed: 15668127
J Immunol Res. 2015;2015:482089
pubmed: 26665156
Medicine (Baltimore). 2019 Oct;98(42):e17506
pubmed: 31626107
Science. 2020 Sep 25;369(6511):1637-1643
pubmed: 32820060
Clin Transl Immunology. 2019 May 11;8(5):e1049
pubmed: 31110702
Cancer Res. 2012 Apr 1;72(7):1844-52
pubmed: 22315351
Nat Biotechnol. 2018 Oct;36(9):847-856
pubmed: 30102295
Haematologica. 2020 Jan 09;106(1):173-184
pubmed: 31919085
Angew Chem Int Ed Engl. 2016 Jun 20;55(26):7520-4
pubmed: 27145250
Front Immunol. 2019 Oct 11;10:2250
pubmed: 31681259
Nat Biotechnol. 2020 Sep;38(9):1012
pubmed: 32887972
Comput Struct Biotechnol J. 2016 Sep 28;14:357-362
pubmed: 27761200
Front Immunol. 2018 Aug 31;9:1977
pubmed: 30233579
Blood Adv. 2019 Nov 12;3(21):3248-3260
pubmed: 31698455
Proc Natl Acad Sci U S A. 2019 Apr 16;116(16):7624-7631
pubmed: 30936321
Mol Ther Oncolytics. 2016 May 18;3:16014
pubmed: 27231717
Biol Blood Marrow Transplant. 2010 Sep;16(9):1245-56
pubmed: 20304086
Proc Natl Acad Sci U S A. 1989 Dec;86(24):10024-8
pubmed: 2513569
Mol Ther. 2017 Sep 6;25(9):2189-2201
pubmed: 28676342
Nat Biotechnol. 2002 Jan;20(1):70-5
pubmed: 11753365
Clin Cancer Res. 2017 May 1;23(9):2267-2276
pubmed: 27803044
Cancer Immunol Res. 2015 Apr;3(4):356-67
pubmed: 25600436
J Cell Physiol. 2019 Jun;234(6):8509-8521
pubmed: 30520029
J Am Chem Soc. 2015 Mar 4;137(8):2832-5
pubmed: 25692571
Cell Immunol. 2016 Jun-Jul;304-305:49-54
pubmed: 26996927
Mol Ther. 2018 Jan 3;26(1):31-44
pubmed: 29103912
Biomark Res. 2020 May 13;8:14
pubmed: 32435496
Lancet Oncol. 2019 Jan;20(1):31-42
pubmed: 30518502
J Biol Chem. 2009 Jan 30;284(5):3273-3284
pubmed: 19010777
Int J Mol Sci. 2020 Jan 30;21(3):
pubmed: 32019116
Mol Ther. 2015 Apr;23(4):769-78
pubmed: 25582824
Clin Exp Immunol. 1998 Apr;112(1):152-8
pubmed: 9566804
Mol Ther. 2010 Apr;18(4):843-51
pubmed: 20179677
Nature. 2017 Mar 2;543(7643):113-117
pubmed: 28225754
Neuro Oncol. 2018 Mar 27;20(4):506-518
pubmed: 29016929
Biochim Biophys Acta. 2014 Jan;1840(1):378-86
pubmed: 24076235
Oncoimmunology. 2015 Jan 23;4(3):e994446
pubmed: 25949921
Cancer Immunol Res. 2020 Apr;8(4):518-529
pubmed: 32019780
J Control Release. 2020 Mar 10;319:246-261
pubmed: 31899268
J Clin Invest. 2016 Jun 1;126(6):2123-38
pubmed: 27111235
Cancers (Basel). 2020 Apr 26;12(5):
pubmed: 32357417
Neoplasia. 1999 Jun;1(2):123-7
pubmed: 10933046
Front Immunol. 2020 May 12;11:888
pubmed: 32477359
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3360-5
pubmed: 19211796
Nat Commun. 2020 Jan 15;11(1):283
pubmed: 31941907
J Immunol. 2007 Apr 1;178(7):4650-7
pubmed: 17372024
Nat Med. 2019 Sep;25(9):1408-1414
pubmed: 31477906
Nat Med. 2015 May;21(5):524-9
pubmed: 25849134
Ther Adv Hematol. 2019 Apr 15;10:2040620719841581
pubmed: 31019670
Biochem Biophys Res Commun. 2020 Jun 25;527(2):350-357
pubmed: 32216966
Ther Adv Hematol. 2020 Jan 29;11:2040620720902899
pubmed: 32064069
Cell. 2018 Oct 4;175(2):313-326
pubmed: 30290139
Nat Med. 2018 Jan;24(1):20-28
pubmed: 29155426
Science. 2013 Dec 20;342(6165):1432-3
pubmed: 24357284
Leukemia. 2017 Oct;31(10):2191-2199
pubmed: 28202953
Int J Mol Sci. 2019 Dec 10;20(24):
pubmed: 31835562
J Immunol. 2013 Sep 1;191(5):2437-45
pubmed: 23898037
Blood. 2018 Feb 15;131(7):746-758
pubmed: 29284597
Annu Rev Pharmacol Toxicol. 2015;55:489-511
pubmed: 25562645
Cancer Res. 2012 Jan 1;72(1):271-81
pubmed: 22075555
J Exp Med. 1998 Aug 17;188(4):619-26
pubmed: 9705944
J Lab Clin Med. 1994 Mar;123(3):365-71
pubmed: 8133147
Sci Transl Med. 2016 Sep 7;8(355):355ra116
pubmed: 27605551
Hum Gene Ther. 2018 May;29(5):585-601
pubmed: 29641319
Oncoimmunology. 2016 Nov 8;5(12):e1253656
pubmed: 28180032
Leukemia. 2016 Jun;30(6):1355-64
pubmed: 26898190
Blood. 2019 Dec 26;134(26):2361-2368
pubmed: 31650176
Nat Med. 2018 Mar;24(3):352-359
pubmed: 29400710
Mol Ther. 2017 Aug 2;25(8):1946-1958
pubmed: 28506593
Hum Gene Ther. 2017 Dec;28(12):1147-1157
pubmed: 29207878
Cell. 2016 Feb 11;164(4):770-9
pubmed: 26830879
Cancer Immunol Res. 2015 Feb;3(2):125-35
pubmed: 25212991
Nat Biotechnol. 2013 Jan;31(1):71-5
pubmed: 23242161
Sci Am. 1996 Sep;275(3):136-43
pubmed: 8701283
Mol Ther. 2015 Apr;23(4):757-68
pubmed: 25366031
Nat Rev Drug Discov. 2015 Jul;14(7):499-509
pubmed: 26129802
Nat Commun. 2020 May 8;11(1):2283
pubmed: 32385241
Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):E6623-E6631
pubmed: 28739923
Annu Rev Biochem. 2013;82:775-97
pubmed: 23495938
Mol Ther. 2017 Nov 1;25(11):2466-2476
pubmed: 28784559
Cell Res. 2017 Jan;27(1):38-58
pubmed: 28025979
Adv Biosci Biotechnol. 2013 Apr;4(4a):73-84
pubmed: 25635232
Immunol Cell Biol. 2013 Jul;91(6):435-40
pubmed: 23628805
Mol Ther. 2018 Jun 6;26(6):1447-1456
pubmed: 29678657
Clin Cancer Res. 2017 Jan 15;23(2):441-453
pubmed: 27435394
Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E450-8
pubmed: 26759368
Theranostics. 2019 Oct 15;9(25):7772-7791
pubmed: 31695800
Blood. 2006 Jun 15;107(12):4669-77
pubmed: 16514054
Proc Natl Acad Sci U S A. 2019 May 7;116(19):9543-9551
pubmed: 30988175
Cells. 2019 May 17;8(5):
pubmed: 31108883
N Engl J Med. 2017 Dec 28;377(26):2545-2554
pubmed: 29226764
Blood. 2013 Feb 14;121(7):1165-74
pubmed: 23243285
Oncoimmunology. 2017 Jun 20;6(10):e1342909
pubmed: 29123951
Mol Ther. 2018 Dec 5;26(12):2727-2737
pubmed: 30309819
Br J Cancer. 2019 Jan;120(1):79-87
pubmed: 30429531
J Clin Oncol. 2018 Aug 1;36(22):2267-2280
pubmed: 29812997
J Hematol Oncol. 2016 Mar 16;9:27
pubmed: 26983639
Oncoimmunology. 2017 Feb 6;6(4):e1287246
pubmed: 28507794
Annu Rev Immunol. 2013;31:413-41
pubmed: 23298206
Cancer Immunol Res. 2014 Mar;2(3):249-62
pubmed: 24778321
PLoS One. 2012;7(2):e31210
pubmed: 22355347
Clin Cancer Res. 2018 Dec 15;24(24):6185-6194
pubmed: 30097433
Nat Rev Cancer. 2019 Aug;19(8):465-478
pubmed: 31278396
Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E459-68
pubmed: 26759369
Semin Oncol. 2014 Oct;41(5):661-6
pubmed: 25440610
J Cell Biochem. 2019 Jun;120(6):10787-10795
pubmed: 30672018
Blood Cancer J. 2016 Aug 12;6(8):e458
pubmed: 27518241
Expert Opin Biol Ther. 2013 Aug;13(8):1149-60
pubmed: 23675652
Sci Transl Med. 2017 Jul 19;9(399):
pubmed: 28724573
Clin Cancer Res. 2019 May 1;25(9):2915-2924
pubmed: 30617136
Oncologist. 2020 Feb;25(2):e321-e327
pubmed: 32043764
Cell Rep. 2017 Oct 3;21(1):17-26
pubmed: 28978471
IUBMB Life. 2019 Sep;71(9):1259-1267
pubmed: 30724452
Med Res Rev. 2022 Jan;42(1):306-342
pubmed: 34028069
Front Immunol. 2018 Oct 26;9:2486
pubmed: 30416506
Cancer Cell. 2015 Oct 12;28(4):415-428
pubmed: 26461090
Cancer Immunol Res. 2018 Jan;6(1):36-46
pubmed: 29180536
Clin Cancer Res. 2019 Feb 15;25(4):1142-1146
pubmed: 30309857
Nat Rev Cancer. 2014 Feb;14(2):135-46
pubmed: 24457417
J Clin Invest. 2011 May;121(5):1822-6
pubmed: 21540550
Clin Cancer Res. 2019 Dec 15;25(24):7506-7516
pubmed: 31548346
Nat Commun. 2019 May 7;10(1):2087
pubmed: 31064990
Nat Commun. 2023 May 9;14(1):2463
pubmed: 37160880
Clin Cancer Res. 2015 Sep 15;21(18):4062-72
pubmed: 26059190
Hybridoma (Larchmt). 2009 Apr;28(2):85-92
pubmed: 19249993
J Immunother Cancer. 2017 May 16;5:42
pubmed: 28515942
J Immunother Cancer. 2018 Dec 4;6(1):137
pubmed: 30514386
Mol Ther. 2007 Apr;15(4):825-33
pubmed: 17299405
Blood. 2011 Apr 21;117(16):4304-14
pubmed: 21304103
Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):720-4
pubmed: 8421711
Pharmacol Ther. 2020 Jan;205:107419
pubmed: 31629009
Hum Gene Ther. 2010 Jan;21(1):75-86
pubmed: 19719389
Science. 2006 Oct 6;314(5796):126-9
pubmed: 16946036
Sci China Life Sci. 2016 Apr;59(4):386-97
pubmed: 26961900
Cancer Immunol Res. 2015 Apr;3(4):368-79
pubmed: 25576337
Blood Adv. 2020 Feb 11;4(3):560-572
pubmed: 32045475
Oncoimmunology. 2017 Oct 26;7(1):e1368604
pubmed: 29296519
Cancer Res. 2015 Sep 1;75(17):3596-607
pubmed: 26330166
Cancer Discov. 2013 Apr;3(4):388-98
pubmed: 23550147
Nat Rev Clin Oncol. 2020 Mar;17(3):147-167
pubmed: 31848460
Cancer Immunol Res. 2016 Jun;4(6):498-508
pubmed: 27059623
Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6106-15
pubmed: 17062687
J Immunol. 2008 May 15;180(10):7028-38
pubmed: 18453625
J Clin Immunol. 2012 Oct;32(5):1059-70
pubmed: 22526592
Blood. 2020 Jan 2;135(1):17-27
pubmed: 31697824
Nat Biotechnol. 2019 Sep;37(9):969-971
pubmed: 31485043
Biochim Biophys Acta. 2014 Nov;1844(11):1983-2001
pubmed: 25065345
Gene Ther. 2010 Oct;17(10):1206-13
pubmed: 20555360
Blood. 2011 Jan 6;117(1):72-82
pubmed: 20889925
Int J Mol Sci. 2019 Mar 14;20(6):
pubmed: 30875739
Cell. 2018 May 31;173(6):1426-1438.e11
pubmed: 29706540
Sci Rep. 2017 Oct 30;7(1):14366
pubmed: 29085043
Mol Med. 2012 May 09;18:565-76
pubmed: 22354215
J Immunother Emphasis Tumor Immunol. 1993 Oct;14(3):182-90
pubmed: 8297900
Mol Pharm. 2018 Oct 1;15(10):4577-4588
pubmed: 30185037
JCI Insight. 2018 Jan 11;3(1):
pubmed: 29321369
J Clin Oncol. 2015 May 10;33(14):1543-50
pubmed: 25823737
J Immunol. 2008 Apr 1;180(7):4901-9
pubmed: 18354214
Cell. 2019 Oct 31;179(4):880-894.e10
pubmed: 31668804
Transfus Med Rev. 2016 Jul;30(3):139-45
pubmed: 27067907
Clin Cancer Res. 2013 Jun 15;19(12):3153-64
pubmed: 23620405
Gut. 2019 Jun;68(6):1052-1064
pubmed: 30121627
Mol Ther Oncolytics. 2018 Nov 06;11:127-137
pubmed: 30581986
J Immunol. 2009 Dec 1;183(11):6939-47
pubmed: 19915047
J Immunol. 2013 Mar 1;190(5):2455-63
pubmed: 23355740
Gene Ther. 2011 May;18(5):509-16
pubmed: 21209626
Blood. 2020 Mar 5;135(10):713-723
pubmed: 31951650