A Novel Siglec-4 Derived Spacer Improves the Functionality of CAR T Cells Against Membrane-Proximal Epitopes.
Animals
Antigens, CD20
/ genetics
Carcinoma, Pancreatic Ductal
/ immunology
Cell Line, Tumor
Cytokines
/ immunology
Disease Models, Animal
HEK293 Cells
Humans
Immunotherapy, Adoptive
Lymphoma
/ immunology
Mice, Inbred NOD
Mice, SCID
Myelin-Associated Glycoprotein
/ genetics
Pancreatic Neoplasms
/ immunology
Phenotype
Receptors, Chimeric Antigen
/ genetics
T-Lymphocytes
/ immunology
Tumor Burden
Xenograft Model Antitumor Assays
CAR design
CH2-CH3
IgG
Siglec
chimeric antigen receptor
hinge
spacer
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
03
03
2020
accepted:
25
06
2020
entrez:
28
8
2020
pubmed:
28
8
2020
medline:
13
4
2021
Statut:
epublish
Résumé
A domain that is often neglected in the assessment of chimeric antigen receptor (CAR) functionality is the extracellular spacer module. However, several studies have elucidated that membrane proximal epitopes are best targeted through CARs comprising long spacers, while short spacer CARs exhibit highest activity on distal epitopes. This finding can be explained by the requirement to have an optimal distance between the effector T cell and target cell. Commonly used long spacer domains are the CH2-CH3 domains of IgG molecules. However, CARs containing these spacers generally show inferior
Identifiants
pubmed: 32849600
doi: 10.3389/fimmu.2020.01704
pmc: PMC7426717
doi:
Substances chimiques
Antigens, CD20
0
Cytokines
0
Myelin-Associated Glycoprotein
0
Receptors, Chimeric Antigen
0
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1704Informations de copyright
Copyright © 2020 Schäfer, Henze, Pfeifer, Schleicher, Brauner, Mockel-Tenbrinck, Barth, Gudert, Al Rawashdeh, Johnston and Hardt.
Références
J Immunol. 2003 Aug 1;171(3):1128-32
pubmed: 12874197
N Engl J Med. 2016 Dec 29;375(26):2561-9
pubmed: 28029927
Proc Natl Acad Sci U S A. 1987 Jan;84(2):600-4
pubmed: 2432614
Mol Cell. 1998 Apr;1(5):719-28
pubmed: 9660955
Neuron. 1994 Oct;13(4):805-11
pubmed: 7524558
Nat Med. 2019 Sep;25(9):1408-1414
pubmed: 31477906
Blood. 2012 Apr 26;119(17):3940-50
pubmed: 22308288
Trends Immunol. 2001 Jun;22(6):337-42
pubmed: 11377294
J Clin Oncol. 2015 Feb 20;33(6):540-9
pubmed: 25154820
J Clin Invest. 2011 May;121(5):1822-6
pubmed: 21540550
Nat Rev Immunol. 2007 Apr;7(4):255-66
pubmed: 17380156
J Immunol. 1998 Apr 15;160(8):3631-6
pubmed: 9558061
N Engl J Med. 2018 Feb 1;378(5):439-448
pubmed: 29385370
Nat Rev Immunol. 2014 Oct;14(10):653-66
pubmed: 25234143
Mol Ther. 2016 Jun;24(6):1135-1149
pubmed: 27019998
J Neurosci. 2009 May 6;29(18):5768-83
pubmed: 19420245
Exp Hematol. 2008 Oct;36(10):1318-28
pubmed: 18599182
J Cell Biol. 1997 Sep 22;138(6):1355-66
pubmed: 9298990
Blood. 2002 May 1;99(9):3256-62
pubmed: 11964291
Mol Ther. 2016 Feb;24(2):354-363
pubmed: 26514825
Neuron. 2002 Jul 18;35(2):283-90
pubmed: 12160746
Gene Ther. 2015 May;22(5):391-403
pubmed: 25652098
Lancet. 2015 Feb 7;385(9967):517-528
pubmed: 25319501
Oncotarget. 2016 Jul 12;7(28):43281-43294
pubmed: 27248327
Cancer Res. 2015 Sep 1;75(17):3505-18
pubmed: 26330164
Glia. 2000 Jan 15;29(2):154-65
pubmed: 10625334
Cancer J. 2014 Mar-Apr;20(2):119-22
pubmed: 24667956
J Immunother. 2005 May-Jun;28(3):203-11
pubmed: 15838376
J Exp Med. 1997 Aug 29;186(5):757-66
pubmed: 9271591
Gene Ther. 1995 Oct;2(8):539-46
pubmed: 8593604
Theranostics. 2017 Apr 5;7(6):1499-1510
pubmed: 28529633
J Immunol. 2003 Mar 1;170(5):2442-8
pubmed: 12594268
Sci Transl Med. 2013 Mar 20;5(177):177ra38
pubmed: 23515080
Blood. 2008 Sep 15;112(6):2261-71
pubmed: 18509084
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
Blood. 2017 Nov 23;130(21):2295-2306
pubmed: 28924019
J Immunol. 2007 Oct 1;179(7):4910-8
pubmed: 17878391
Cell. 1992 Mar 20;68(6):1145-62
pubmed: 1547508
J Neurosci. 2005 Jan 26;25(4):808-22
pubmed: 15673660
J Clin Invest. 2016 Jun 1;126(6):2123-38
pubmed: 27111235
Eur J Immunol. 2005 Mar;35(3):776-85
pubmed: 15714585
Oncoimmunology. 2016 Nov 8;5(12):e1253656
pubmed: 28180032
Cancer Immunol Res. 2015 Feb;3(2):125-35
pubmed: 25212991
Mol Ther. 2015 Apr;23(4):757-68
pubmed: 25366031
Dev Comp Immunol. 2018 Sep;86:219-231
pubmed: 29751010
Eur J Immunol. 1998 May;28(5):1663-72
pubmed: 9603473
J Comp Neurol. 1989 Jun 15;284(3):451-62
pubmed: 2474006
Eur J Immunol. 1996 Sep;26(9):2012-6
pubmed: 8814239
N Engl J Med. 2017 Dec 28;377(26):2545-2554
pubmed: 29226764
Blood. 2013 Feb 14;121(7):1165-74
pubmed: 23243285
Gene Ther. 1999 Mar;6(3):412-9
pubmed: 10435091
Neuron. 1994 Sep;13(3):757-67
pubmed: 7522484
Glycobiology. 2004 Nov;14(11):959-68
pubmed: 15229193
Sci Transl Med. 2015 Sep 2;7(303):303ra139
pubmed: 26333935
Proc Natl Acad Sci U S A. 2002 May 14;99(10):7009-14
pubmed: 11997459
Biol Blood Marrow Transplant. 1998;4(2):75-83
pubmed: 9763110
Trends Immunol. 2015 Aug;36(8):494-502
pubmed: 26169254
Blood. 2006 Mar 15;107(6):2294-302
pubmed: 16282341
Immunity. 2000 Apr;12(4):409-18
pubmed: 10795739
Nature. 2015 Dec 10;528(7581):225-30
pubmed: 26605524
J Immunol Methods. 2001 Feb 1;248(1-2):67-76
pubmed: 11223069
J Neurosci. 2007 Aug 22;27(34):9146-54
pubmed: 17715351
Hum Gene Ther. 2017 Oct;28(10):914-925
pubmed: 28847167
Science. 2002 Aug 16;297(5584):1190-3
pubmed: 12089450
Blood. 2016 Jun 16;127(24):2980-90
pubmed: 27118452
Structure. 2003 May;11(5):557-67
pubmed: 12737821
Cancer Immunol Res. 2015 Apr;3(4):368-79
pubmed: 25576337
J Leukoc Biol. 2006 Jan;79(1):46-58
pubmed: 16380601
Eur J Immunol. 2009 Oct;39(10):2716-24
pubmed: 19658094
J Immunol. 2008 May 15;180(10):7028-38
pubmed: 18453625
Nat Med. 1996 Feb;2(2):216-23
pubmed: 8574968
J Biol Chem. 1999 Dec 31;274(53):37637-43
pubmed: 10608819
N Engl J Med. 2018 Feb 1;378(5):449-459
pubmed: 29385376
Proc Natl Acad Sci U S A. 1987 Jun;84(12):4337-41
pubmed: 2438699
N Engl J Med. 2017 Dec 28;377(26):2531-2544
pubmed: 29226797
Gene Ther. 2010 Oct;17(10):1206-13
pubmed: 20555360
Blood. 2016 Jun 30;127(26):3321-30
pubmed: 27207799
Science. 2008 Nov 7;322(5903):967-70
pubmed: 18988857
N Engl J Med. 2013 Apr 18;368(16):1509-1518
pubmed: 23527958
Prostate. 2007 Jul 1;67(10):1121-31
pubmed: 17492652
Glycobiology. 2011 Jun;21(6):757-70
pubmed: 21278227
Clin Cancer Res. 2013 Jun 15;19(12):3153-64
pubmed: 23620405
J Cell Biol. 1989 Nov;109(5):2417-26
pubmed: 2478568