The peculiar challenge of bringing CAR-T cells into the brain: Perspectives in the clinical application to the treatment of pediatric central nervous system tumors.
CAR-T cells
blood-brain barrier
glymphatic system
neurotoxicity
pediatric brain tumors
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:
11
01
2023
accepted:
09
03
2023
medline:
10
4
2023
entrez:
7
4
2023
pubmed:
8
4
2023
Statut:
epublish
Résumé
Childhood malignant brain tumors remain a significant cause of death in the pediatric population, despite the use of aggressive multimodal treatments. New therapeutic approaches are urgently needed for these patients in order to improve prognosis, while reducing side effects and long-term sequelae of the treatment. Immunotherapy is an attractive option and, in particular, the use of gene-modified T cells expressing a chimeric antigen receptor (CAR-T cells) represents a promising approach. Major hurdles in the clinical application of this approach in neuro-oncology, however, exist. The peculiar location of brain tumors leads to both a difficulty of access to the tumor mass, shielded by the blood-brain barrier (BBB), and to an increased risk of potentially life-threatening neurotoxicity, due to the primary location of the disease in the CNS and the low intracranial volume reserve. There are no unequivocal data on the best way of CAR-T cell administration. Multiple trials exploring the use of CD19 CAR-T cells for hematologic malignancies proved that genetically engineered T cells can cross the BBB, suggesting that systemically administered CAR-T cell can be used in the neuro-oncology setting. Intrathecal and intra-tumoral delivery can be easily managed with local implantable devices, suitable also for a more precise neuro-monitoring. The identification of specific approaches of neuro-monitoring is of utmost importance in these patients. In the present review, we highlight the most relevant potential challenges associated with the application of CAR-T cell therapy in pediatric brain cancers, focusing on the evaluation of the best route of delivery, the peculiar risk of neurotoxicity and the related neuro-monitoring.
Identifiants
pubmed: 37025994
doi: 10.3389/fimmu.2023.1142597
pmc: PMC10072260
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1142597Informations de copyright
Copyright © 2023 Del Baldo, Del Bufalo, Pinacchio, Carai, Quintarelli, De Angelis, Merli, Cacchione, Locatelli and Mastronuzzi.
Déclaration de conflit d'intérêts
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
Adv Cell Gene Ther. 2018 Sep;1(2):
pubmed: 30420973
N Engl J Med. 2016 Dec 29;375(26):2561-9
pubmed: 28029927
Am J Pathol. 2000 Jan;156(1):139-50
pubmed: 10623661
N Engl J Med. 2018 Feb 1;378(5):439-448
pubmed: 29385370
Nat Med. 2015 Jun;21(6):581-90
pubmed: 25939063
Transfus Med Hemother. 2019 Feb;46(1):4-13
pubmed: 31244577
NPJ Precis Oncol. 2023 Feb 15;7(1):17
pubmed: 36792722
Nat Immunol. 2011 Jun;12(6):492-9
pubmed: 21739672
J Clin Invest. 2016 Aug 1;126(8):3036-52
pubmed: 27427982
Front Oncol. 2020 Aug 12;10:1582
pubmed: 32903405
Leuk Lymphoma. 2019 Nov;60(11):2606-2621
pubmed: 31092071
Cells. 2018 Aug 17;7(8):
pubmed: 30126117
Intensive Care Med. 2015 Sep;41(9):1517-28
pubmed: 26194024
J Cell Biochem. 2000 Apr;78(1):85-96
pubmed: 10797568
Neurosurg Focus. 2012 Jan;32(1):E3
pubmed: 22208896
N Engl J Med. 2014 Oct 16;371(16):1507-17
pubmed: 25317870
Brain Pathol. 2014 Mar;24(2):117-27
pubmed: 23944716
Neuro Oncol. 2021 Jun 1;23(6):999-1011
pubmed: 33320196
Crit Care. 2019 Jun 7;23(1):209
pubmed: 31174580
J Exp Med. 2007 Sep 3;204(9):2023-30
pubmed: 17682068
Hum Gene Ther. 2012 Oct;23(10):1043-53
pubmed: 22780919
Mol Ther. 2015 Sep;23(9):1475-85
pubmed: 26022733
Curr Opin Immunol. 2015 Apr;33:55-63
pubmed: 25665467
Nat Biotechnol. 2018 Apr;36(4):346-351
pubmed: 29505028
Expert Opin Biol Ther. 2020 Jun;20(6):653-664
pubmed: 32067497
Cytotherapy. 2003;5(3):211-26
pubmed: 12850789
Cancer Immunol Res. 2014 Feb;2(2):154-66
pubmed: 24778279
Mol Ther. 2017 Jan 4;25(1):249-258
pubmed: 28129119
Cancer Res. 2017 Mar 15;77(6):1296-1309
pubmed: 28082401
Nat Immunol. 2008 Feb;9(2):137-45
pubmed: 18157132
Nat Rev Neurol. 2013 Jul;9(7):405-15
pubmed: 23752906
Proc Natl Acad Sci U S A. 1989 Dec;86(24):10024-8
pubmed: 2513569
Nat Biotechnol. 2002 Jan;20(1):70-5
pubmed: 11753365
Nat Med. 2019 Mar;25(3):470-476
pubmed: 30742120
Eur J Cancer. 2015 Nov;51(17):2634-42
pubmed: 26346136
Cancer Immunol Res. 2019 May;7(5):759-772
pubmed: 30890531
Mol Ther. 2018 Jan 3;26(1):31-44
pubmed: 29103912
Nature. 2016 Feb 18;530(7590):349-53
pubmed: 26863192
Neuro Oncol. 2018 Mar 27;20(4):506-518
pubmed: 29016929
Trends Immunol. 2012 Dec;33(12):579-89
pubmed: 22926201
Brain Sci. 2017 Oct 21;7(10):
pubmed: 29065490
J Immunother. 2019 May;42(4):126-135
pubmed: 30882547
Transfus Med Rev. 2019 Apr;33(2):98-110
pubmed: 30948292
J Clin Invest. 2016 Jun 1;126(6):2123-38
pubmed: 27111235
Blood Rev. 2016 May;30(3):157-67
pubmed: 26574053
Results Probl Cell Differ. 2006;43:259-80
pubmed: 17068976
Stem Cell Reports. 2018 Sep 11;11(3):795-810
pubmed: 30122444
Clin Cancer Res. 2012 Mar 15;18(6):1672-83
pubmed: 22291136
Cancer Immunol Res. 2016 Feb;4(2):124-35
pubmed: 26546453
Childs Nerv Syst. 2017 Oct;33(10):1745-1750
pubmed: 29149391
Blood. 2013 Jan 24;121(4):573-84
pubmed: 23160470
Nat Med. 2015 May;21(5):524-9
pubmed: 25849134
Cancer Cell. 2017 Mar 13;31(3):326-341
pubmed: 28292436
Neuro Oncol. 2018 Jan 10;20(1):55-65
pubmed: 28651374
J Clin Oncol. 2017 Jul 20;35(21):2450-2456
pubmed: 28640704
Clin Cancer Res. 2011 Jul 15;17(14):4719-30
pubmed: 21610146
J Natl Cancer Inst. 2016 Jan 27;108(7):
pubmed: 26819347
Nat Biotechnol. 2018 Sep;36(8):707-716
pubmed: 29985479
Acta Neurol Scand. 2016 Sep;134(3):168-80
pubmed: 26666840
Cancer Gene Ther. 2022 Aug;29(8-9):1080-1096
pubmed: 34987176
Clin Cancer Res. 2007 Apr 1;13(7):2158-67
pubmed: 17404100
Adv Radiat Oncol. 2018 Oct 23;3(4):520-526
pubmed: 30370351
Leukemia. 2006 Oct;20(10):1819-28
pubmed: 16932339
J Neurosci Methods. 2013 Apr 15;214(2):223-32
pubmed: 23419699
Blood. 2017 Feb 23;129(8):1039-1041
pubmed: 28031179
J Clin Invest. 2010 May;120(5):1368-79
pubmed: 20440079
Immunol Rev. 2019 Jul;290(1):60-84
pubmed: 31355493
Blood. 2002 May 1;99(9):3179-87
pubmed: 11964281
J Neurooncol. 2017 Oct;135(1):13-20
pubmed: 28681244
Nat Genet. 2012 May 29;44(6):619-22
pubmed: 22641210
ACS Chem Neurosci. 2018 Jan 17;9(1):11-28
pubmed: 29199818
J Neurosci Methods. 2016 Feb 1;259:47-56
pubmed: 26617320
Mol Cell. 2019 Jul 11;75(1):7-12
pubmed: 31299208
Leg Med (Tokyo). 2008 Nov;10(6):293-300
pubmed: 18658002
Leukemia. 2004 Apr;18(4):676-84
pubmed: 14961035
Nat Rev Cancer. 2014 Aug;14(8):559-67
pubmed: 24990523
J Hematol Oncol. 2022 Nov 5;15(1):163
pubmed: 36335396
Nat Neurosci. 2011 Jul 31;14(9):1142-9
pubmed: 21804537
Cancer Cell. 2017 Apr 10;31(4):476-485
pubmed: 28366678
J Child Neurol. 2016 Mar;31(4):488-505
pubmed: 26245798
Front Oncol. 2021 Oct 25;11:718030
pubmed: 34760690
Clin Cancer Res. 2009 Dec 1;15(23):7412-20
pubmed: 19934295
Oncoimmunology. 2015 Oct 29;5(3):e1105428
pubmed: 27195186
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3525-9
pubmed: 8622970
Nat Med. 2021 Sep;27(9):1544-1552
pubmed: 34253928
Gerontology. 2019;65(2):106-119
pubmed: 29996134
Nature. 2015 Jul 16;523(7560):337-41
pubmed: 26030524
Nat Rev Immunol. 2018 Apr;18(4):225-242
pubmed: 29151590
Oncotarget. 2017 Sep 23;8(54):92275-92288
pubmed: 29190914
Mol Ther. 2018 Jul 5;26(7):1855-1866
pubmed: 29807781
Cell. 2019 Aug 8;178(4):835-849.e21
pubmed: 31327527
Pediatr Neurosurg. 2020;55(1):54-57
pubmed: 31722365
N Engl J Med. 2017 Oct 5;377(14):1345-1356
pubmed: 28889792
Brain Res. 2005 Mar 21;1038(2):208-15
pubmed: 15757636
Nat Neurosci. 2017 Feb;20(2):136-144
pubmed: 28092660
Sci Rep. 2017 Jan 20;7:39833
pubmed: 28106050
Cancer Treat Rev. 2017 Jul;58:22-33
pubmed: 28622628
Nature. 2018 Mar 15;555(7696):321-327
pubmed: 29489754
Childs Nerv Syst. 2016 Apr;32(4):703-7
pubmed: 26597683
Ann Transl Med. 2017 Dec;5(23):462
pubmed: 29285495
Neuron. 2018 Jun 27;98(6):1170-1183.e8
pubmed: 29861285
Sci Transl Med. 2017 Jul 19;9(399):
pubmed: 28724573
Mol Ther. 2017 Nov 1;25(11):2440-2451
pubmed: 28974431
Cancer Res. 2012 Feb 15;72(4):917-27
pubmed: 22186141
Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7788-E7797
pubmed: 27849617
Clin Cancer Res. 2013 Sep 15;19(18):4951-60
pubmed: 23864165
J Clin Invest. 2011 May;121(5):1822-6
pubmed: 21540550
J Neurooncol. 2012 Jul;108(3):395-402
pubmed: 22382786
Neurosurg Focus. 2018 Feb;44(2):E10
pubmed: 29385922
J Neurosurg Pediatr. 2014 Mar;13(3):301-6
pubmed: 24404968
Front Immunol. 2017 Sep 25;8:1181
pubmed: 28993773
Cancer Cell. 2021 Jun 14;39(6):779-792.e11
pubmed: 34087162
Cancer Discov. 2017 Nov;7(11):1238-1247
pubmed: 28830878
Cytotherapy. 2020 Oct;22(10):552-562
pubmed: 32747298
Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):720-4
pubmed: 8421711
Pediatr Blood Cancer. 2014 Sep;61(9):1590-2
pubmed: 24777835
Clin Cancer Res. 2017 May 1;23(9):2255-2266
pubmed: 27815355
Clin Cancer Res. 2019 Apr 15;25(8):2560-2574
pubmed: 30655315
Cancers (Basel). 2022 Oct 18;14(20):
pubmed: 36291891
J Neurosurg Pediatr. 2019 Mar 1;23(3):261-273
pubmed: 30835699
J Neurooncol. 2019 Aug;144(1):33-41
pubmed: 31197598
Nat Rev Cancer. 2019 Aug;19(8):420-438
pubmed: 31300807
Nat Genet. 2019 Feb;51(2):202-206
pubmed: 30643254
Nature. 2022 Mar;603(7903):934-941
pubmed: 35130560
Nat Med. 2018 Aug;24(8):1204-1215
pubmed: 29967352
Cancer Lett. 2020 Jun 1;479:13-22
pubmed: 32112904
Neurooncol Pract. 2020 Nov 29;8(3):259-265
pubmed: 34055373