CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
12 11 2020
12 11 2020
Historique:
received:
24
04
2020
accepted:
16
06
2020
pubmed:
3
7
2020
medline:
7
4
2021
entrez:
3
7
2020
Statut:
ppublish
Résumé
Natural killer (NK) cells are a promising cellular immunotherapy for cancer. Cytokine-induced memory-like (ML) NK cells differentiate after activation with interleukin-12 (IL-12), IL-15, and IL-18, exhibit potent antitumor responses, and safely induce complete remissions in patients with leukemia. However, many cancers are not fully recognized via NK cell receptors. Chimeric antigen receptors (CARs) have been used to enhance tumor-specific recognition by effector lymphocytes. We hypothesized that ML differentiation and CAR engineering would result in complementary improvements in NK cell responses against NK-resistant cancers. To test this idea, peripheral blood ML NK cells were modified to express an anti-CD19 CAR (19-CAR-ML), which displayed significantly increased interferon γ production, degranulation, and specific killing against NK-resistant lymphoma lines and primary targets compared with nonspecific control CAR-ML NK cells or conventional CAR NK cells. The 19-CAR and ML responses were synergistic and CAR specific and required immunoreceptor tyrosine-based activation motif signaling. Furthermore, 19-CAR-ML NK cells generated from lymphoma patients exhibited improved responses against their autologous lymphomas. 19-CAR-ML NK cells controlled lymphoma burden in vivo and improved survival in human xenograft models. Thus, CAR engineering of ML NK cells enhanced responses against resistant cancers and warrants further investigation, with the potential to broaden ML NK cell recognition against a variety of NK cell-resistant tumors.
Identifiants
pubmed: 32614951
pii: S0006-4971(20)79931-3
doi: 10.1182/blood.2020006619
pmc: PMC7702478
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2308-2318Subventions
Organisme : NCI NIH HHS
ID : F32 CA200253
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA171963
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205239
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007088
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA167540
Pays : United States
Informations de copyright
© 2020 by The American Society of Hematology.
Références
Immunol Cell Biol. 2017 Apr;95(4):347-355
pubmed: 28138156
Crit Care Med. 2017 Feb;45(2):e124-e131
pubmed: 27632680
Curr Mol Med. 2004 Jun;4(4):431-8
pubmed: 15354873
Blood. 2008 Aug 1;112(3):461-9
pubmed: 18650461
Hematology Am Soc Hematol Educ Program. 2013;2013:234-46
pubmed: 24319186
Mol Ther Oncolytics. 2016 Apr 20;3:16011
pubmed: 27626062
Blood. 2010 May 27;115(21):4293-301
pubmed: 20233969
Blood. 2012 Dec 6;120(24):4751-60
pubmed: 22983442
Leukemia. 2018 Feb;32(2):520-531
pubmed: 28725044
Pharmacol Res Perspect. 2015 Jun;3(3):e00149
pubmed: 26171228
Cancer Immunol Immunother. 2016 Apr;65(4):485-92
pubmed: 26559813
N Engl J Med. 2018 Feb 1;378(5):449-459
pubmed: 29385376
Annu Rev Immunol. 2013;31:227-58
pubmed: 23516982
CNS Drugs. 2018 Dec;32(12):1091-1101
pubmed: 30387077
Clin Immunol. 2017 Apr;177:3-11
pubmed: 26883680
N Engl J Med. 2018 Feb 1;378(5):439-448
pubmed: 29385370
Mol Ther. 2017 Oct 4;25(10):2245-2253
pubmed: 28803861
Front Immunol. 2017 Mar 23;8:329
pubmed: 28386260
Cell Mol Immunol. 2011 Jul;8(4):281-4
pubmed: 21217771
Cancer Discov. 2018 Oct;8(10):1219-1226
pubmed: 30135176
Cold Spring Harb Perspect Biol. 2010 Jun;2(6):a002485
pubmed: 20516133
J Clin Oncol. 2017 Sep 10;35(26):3010-3020
pubmed: 28715249
Curr Opin Organ Transplant. 2015 Dec;20(6):671-80
pubmed: 26414502
Cytotherapy. 2016 May;18(5):653-63
pubmed: 27059202
Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1915-9
pubmed: 19181844
J Exp Med. 2012 Dec 17;209(13):2351-65
pubmed: 23209317
Nat Immunol. 2010 Dec;11(12):1127-35
pubmed: 20972432
Lancet Oncol. 2019 Jan;20(1):31-42
pubmed: 30518502
N Engl J Med. 2020 Feb 6;382(6):545-553
pubmed: 32023374
Cancer Res. 2013 Mar 15;73(6):1777-86
pubmed: 23302231
Semin Cancer Biol. 2006 Oct;16(5):348-58
pubmed: 16893656
Science. 2018 Mar 23;359(6382):1361-1365
pubmed: 29567707
J Immunol. 2015 Sep 15;195(6):2806-17
pubmed: 26268657
Immunity. 2007 Jun;26(6):798-811
pubmed: 17540585
Front Immunol. 2015 Jun 10;6:266
pubmed: 26113846
Nat Rev Immunol. 2001 Oct;1(1):41-9
pubmed: 11905813
Front Pharmacol. 2015 Feb 12;6:21
pubmed: 25729364
J Mol Cell Cardiol. 1998 Apr;30(4):723-31
pubmed: 9602421
J Clin Oncol. 2015 Feb 20;33(6):540-9
pubmed: 25154820
Am J Cancer Res. 2018 Jun 01;8(6):1083-1089
pubmed: 30034945
Sci Transl Med. 2015 Sep 2;7(303):303ra139
pubmed: 26333935
J Immunol. 2002 Oct 15;169(8):4230-6
pubmed: 12370353
Sci Transl Med. 2016 Sep 21;8(357):357ra123
pubmed: 27655849
Trends Immunol. 2016 Dec;37(12):877-888
pubmed: 27773685
Blood. 2005 Apr 15;105(8):3051-7
pubmed: 15632206
Nature. 2009 Jan 29;457(7229):557-61
pubmed: 19136945
Clin Cancer Res. 2016 Feb 1;22(3):596-608
pubmed: 26423796
Cell Stem Cell. 2018 Aug 02;23(2):181-192.e5
pubmed: 30082067
Leukemia. 2015 Aug;29(8):1637-47
pubmed: 25721896
Annu Rev Immunol. 2004;22:405-29
pubmed: 15032583
Annu Rev Immunol. 1998;16:359-93
pubmed: 9597134
Nat Rev Clin Oncol. 2013 May;10(5):267-76
pubmed: 23546520