Highly Efficient Generation of Transgenically Augmented CAR NK Cells Overexpressing CXCR4.
Antigens, Neoplasm
/ immunology
Cell Line, Tumor
Cell Movement
Chemotaxis
/ genetics
Cytotoxicity, Immunologic
Gene Expression
Humans
Immunomodulation
Immunophenotyping
Immunotherapy, Adoptive
/ methods
Killer Cells, Natural
/ immunology
Receptors, Antigen, T-Cell
/ genetics
Receptors, CXCR4
/ genetics
Receptors, Chimeric Antigen
/ genetics
Transduction, Genetic
CD19
chemokine receptor 4
chimeric antigen receptor
fully human CAR
huCAR19
immunotherapy
natural killer cell
transgenically augmented CAR NK cell
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:
23
12
2019
accepted:
27
07
2020
entrez:
28
9
2020
pubmed:
29
9
2020
medline:
1
5
2021
Statut:
epublish
Résumé
Natural killer (NK) cells are a noteworthy lymphocyte subset in cancer adoptive cell therapy. NK cells initiate innate immune responses against infections and malignancies with natural cytotoxicity, which is independent of foreign antigen recognition. Based on these substantive features, genetically modifying NK cells is among the prime goals in immunotherapy but is currently difficult to achieve. Recently, we reported a fully human CAR19 construct (huCAR19) with remarkable function in gene-modified T-cells. Here, we show efficient and stable gene delivery of huCAR19 to primary human NK cells using lentiviral vectors with transduction efficiencies comparable to those achieved with NK cell lines. These huCAR19 NK cells display specific and potent cytotoxic activity against target cells. To improve homing of NK cells to the bone marrow, we augmented huCAR19 NK cells with the human CXCR4 gene, resulting in transgenically augmented CAR NK cells (TRACKs). Compared to conventional CAR NK cells, TRACKs exhibit enhanced migration capacity in response to recombinant SDF-1 or bone marrow stromal cells while retaining functional and cytolytic activity against target cells. Based on these promising findings, TRACKs may become a novel candidate for immunotherapeutic strategies in clinical applications.
Identifiants
pubmed: 32983147
doi: 10.3389/fimmu.2020.02028
pmc: PMC7483584
doi:
Substances chimiques
Antigens, Neoplasm
0
CXCR4 protein, human
0
Receptors, Antigen, T-Cell
0
Receptors, CXCR4
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2028Informations de copyright
Copyright © 2020 Jamali, Hadjati, Madjd, Mirzaei, Thalheimer, Agarwal, Bonig, Ullrich and Hartmann.
Références
J Immunol. 2015 Sep 1;195(5):2493-501
pubmed: 26232436
Front Immunol. 2019 Nov 14;10:2683
pubmed: 31798595
Mol Ther. 2016 Aug;24(7):1237-46
pubmed: 27058824
Exp Hematol. 2014 Nov;42(11):976-986.e3
pubmed: 25179751
Oncoimmunology. 2014 Apr 15;3:e28147
pubmed: 25340009
Curr Opin Immunol. 2018 Apr;51:146-153
pubmed: 29605760
Gene Ther. 2010 Oct;17(10):1244-52
pubmed: 20485382
Transfus Med Hemother. 2019 Feb;46(1):4-13
pubmed: 31244577
Front Immunol. 2018 Feb 15;9:283
pubmed: 29497427
Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17481-6
pubmed: 18987320
Leuk Lymphoma. 2012 May;53(5):958-65
pubmed: 22023526
J Immunother. 2010 Feb-Mar;33(2):200-10
pubmed: 20145545
Front Immunol. 2019 Apr 30;10:957
pubmed: 31114587
Hum Gene Ther. 2012 Oct;23(10):1090-100
pubmed: 22779406
J Virol. 2009 Oct;83(19):9854-62
pubmed: 19625395
Front Immunol. 2020 Jan 24;10:3123
pubmed: 32117200
J Virol. 1998 Nov;72(11):8463-71
pubmed: 9765382
Iran J Allergy Asthma Immunol. 2020 Jun 23;19(3):264-275
pubmed: 32615660
Cytotherapy. 2017 Feb;19(2):235-249
pubmed: 27887866
Front Immunol. 2019 Dec 16;10:2873
pubmed: 31921138
Mol Ther Methods Clin Dev. 2019 Mar 16;13:371-379
pubmed: 30997367
J Immunol Res. 2018 Sep 17;2018:4054815
pubmed: 30306093
Blood. 2008 Apr 1;111(7):3626-34
pubmed: 18227348
N Engl J Med. 2020 Feb 6;382(6):545-553
pubmed: 32023374
J Immunother. 2015 Jun;38(5):197-210
pubmed: 25962108
EMBO Mol Med. 2017 Sep;9(9):1183-1197
pubmed: 28765140
Leukemia. 2017 Oct;31(10):2191-2199
pubmed: 28202953
J Immunother Cancer. 2017 Sep 19;5(1):73
pubmed: 28923105
Front Immunol. 2015 Jun 10;6:266
pubmed: 26113846
Front Immunol. 2019 Jun 05;10:1262
pubmed: 31231387
Blood. 2005 Jul 1;106(1):376-83
pubmed: 15755898
Front Immunol. 2017 May 31;8:631
pubmed: 28620386
Exp Hematol. 1996 Feb;24(3):406-15
pubmed: 8599969
Am J Cancer Res. 2018 Jun 01;8(6):1083-1089
pubmed: 30034945
Mol Ther. 2015 Feb;23(2):330-8
pubmed: 25373520
Mol Ther. 2017 Aug 2;25(8):1769-1781
pubmed: 28668320
Haematologica. 2016 Aug;101(8):985-94
pubmed: 27175026
Cancer Cell. 2017 Sep 11;32(3):324-341.e6
pubmed: 28870739
J Clin Invest. 2018 May 1;128(5):2010-2024
pubmed: 29485974
J Exp Clin Cancer Res. 2020 Mar 10;39(1):49
pubmed: 32151275
Blood. 2011 Nov 3;118(18):4863-71
pubmed: 21911833
J Cell Mol Med. 2018 Dec;22(12):5776-5786
pubmed: 30255991
Sci Rep. 2015 Jul 09;5:11483
pubmed: 26155832
J Cell Physiol. 2019 Jun;234(6):9207-9215
pubmed: 30362586
Front Immunol. 2016 Oct 06;7:402
pubmed: 27766097