Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform.
Animals
Antibodies, Anti-Idiotypic
/ immunology
HEK293 Cells
HIV Infections
/ genetics
HIV-1
/ immunology
Humans
Immunotherapy, Adoptive
Mice
Palatine Tonsil
/ immunology
Primary Cell Culture
Spleen
/ immunology
T-Lymphocytes, Cytotoxic
/ immunology
Virus Latency
/ immunology
Virus Replication
/ genetics
CAR-T
HIV latency
MicAbody
T cell therapy
bNAb
broadly neutralizing HIV antibodies
convertibleCAR-T
reduce-and-control
reservoir
shock-and-kill
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
31 10 2019
31 10 2019
Historique:
received:
16
05
2019
revised:
19
07
2019
accepted:
01
10
2019
entrez:
1
11
2019
pubmed:
2
11
2019
medline:
28
5
2020
Statut:
ppublish
Résumé
Current approaches to reducing the latent HIV reservoir entail first reactivating virus-containing cells to become visible to the immune system. A critical second step is killing these cells to reduce reservoir size. Endogenous cytotoxic T-lymphocytes (CTLs) may not be adequate because of cellular exhaustion and the evolution of CTL-resistant viruses. We have designed a universal CAR-T cell platform based on CTLs engineered to bind a variety of broadly neutralizing anti-HIV antibodies. We show that this platform, convertibleCAR-T cells, effectively kills HIV-infected, but not uninfected, CD4 T cells from blood, tonsil, or spleen and only when armed with anti-HIV antibodies. convertibleCAR-T cells also kill within 48 h more than half of the inducible reservoir found in blood of HIV-infected individuals on antiretroviral therapy. The modularity of convertibleCAR-T cell system, which allows multiplexing with several anti-HIV antibodies yielding greater breadth and control, makes it a promising tool for attacking the latent HIV reservoir.
Identifiants
pubmed: 31668804
pii: S0092-8674(19)31118-3
doi: 10.1016/j.cell.2019.10.002
pmc: PMC6922308
mid: NIHMS1544021
pii:
doi:
Substances chimiques
Antibodies, Anti-Idiotypic
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
880-894.e10Subventions
Organisme : NIDCR NIH HHS
ID : DP1 DE024408
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI109593
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
Cell. 2010 Nov 24;143(5):789-801
pubmed: 21111238
Nat Med. 2017 Feb;23(2):185-191
pubmed: 28092665
EBioMedicine. 2016 Jun;8:217-229
pubmed: 27428432
Mol Ther Methods Clin Dev. 2018 Dec 31;12:145-156
pubmed: 30666307
Cancer Discov. 2015 Dec;5(12):1282-95
pubmed: 26516065
Nucleic Acids Res. 2014 Jan;42(Database issue):D1133-9
pubmed: 24214957
J Leukoc Biol. 2012 Dec;92(6):1147-54
pubmed: 22802445
Mol Ther. 2018 Oct 3;26(10):2496-2506
pubmed: 30249388
Lancet HIV. 2016 Aug;3(8):e361-e387
pubmed: 27470028
Nat Med. 2019 Apr;25(4):547-553
pubmed: 30936546
Proc Natl Acad Sci U S A. 1988 May;85(10):3570-4
pubmed: 3259321
Nat Med. 2018 May;24(5):604-609
pubmed: 29686423
Immunity. 2008 Dec 19;29(6):1009-21
pubmed: 19062316
Nature. 1993 Mar 25;362(6418):355-8
pubmed: 8455722
Sci Transl Med. 2012 May 2;4(132):132ra53
pubmed: 22553251
Science. 1997 Nov 14;278(5341):1291-5
pubmed: 9360926
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7
pubmed: 9371822
Curr Opin Hematol. 2015 Nov;22(6):509-515
pubmed: 26390167
Immunity. 2012 Mar 23;36(3):491-501
pubmed: 22406268
Cells. 2018 Oct 01;7(10):
pubmed: 30275435
Eur J Immunol. 2010 Apr;40(4):949-54
pubmed: 20201043
Semin Oncol. 2002 Oct;29(5 Suppl 14):18-30
pubmed: 12422310
Retrovirology. 2018 Oct 16;15(1):70
pubmed: 30326938
Hum Vaccin Immunother. 2013 Apr;9(4):790-9
pubmed: 23563519
Cell Host Microbe. 2015 Oct 14;18(4):463-70
pubmed: 26468749
Mol Ther. 2017 Mar 1;25(3):570-579
pubmed: 28143740
Cell. 2015 Feb 26;160(5):990-1001
pubmed: 25723172
J Infect Dis. 2013 Oct 15;208(8):1202-11
pubmed: 23852127
PLoS Pathog. 2017 Feb 16;13(2):e1006163
pubmed: 28207890
Nature. 2016 Jul 28;535(7613):556-60
pubmed: 27338952
J Transl Med. 2011 Jan 27;9 Suppl 1:S5
pubmed: 21284904
Elife. 2018 May 01;7:
pubmed: 29714165
Cytotherapy. 2003;5(3):211-26
pubmed: 12850789
Immunity. 2001 Feb;14(2):123-33
pubmed: 11239445
J Virol. 2002 Sep;76(17):8776-86
pubmed: 12163598
Mol Ther. 2016 Aug;24(7):1178-86
pubmed: 27203439
AIDS. 2016 Sep 24;30(15):2299-302
pubmed: 27428742
Mol Ther. 2017 Sep 6;25(9):2189-2201
pubmed: 28676342
Virology. 2019 Jan 2;526:189-202
pubmed: 30415130
JCI Insight. 2018 Oct 18;3(20):
pubmed: 30333308
Nat Commun. 2016 Mar 03;7:10844
pubmed: 26936020
J Virol. 1999 Aug;73(8):6721-8
pubmed: 10400770
Blood. 1997 Sep 15;90(6):2188-95
pubmed: 9310469
J Virol. 2016 Oct 14;90(21):9712-9724
pubmed: 27535056
Curr HIV/AIDS Rep. 2018 Apr;15(2):147-154
pubmed: 29500712
J Virol. 2017 Mar 29;91(8):
pubmed: 28179531
Nucleic Acids Res. 2013 Jan 7;41(1):277-87
pubmed: 23087374
PLoS Pathog. 2017 Dec 28;13(12):e1006753
pubmed: 29284044
Cold Spring Harb Perspect Med. 2011 Sep;1(1):a007096
pubmed: 22229121
Cell Rep. 2017 Jul 25;20(4):984-998
pubmed: 28746881
J Virol. 1992 Mar;66(3):1354-60
pubmed: 1738194
J Exp Med. 2013 Dec 16;210(13):2813-21
pubmed: 24277152
Mol Ther. 2016 Mar;24(3):570-81
pubmed: 26502778
J Immunol. 2015 Feb 1;194(3):911-20
pubmed: 25520398
J Clin Invest. 2015 Sep;125(9):3477-90
pubmed: 26241055
Mol Ther Oncolytics. 2016 Apr 20;3:16011
pubmed: 27626062
AIDS. 2016 Jan 28;30(3):343-53
pubmed: 26588174
Science. 1997 Nov 14;278(5341):1295-300
pubmed: 9360927
Cell. 2016 Feb 11;164(4):770-9
pubmed: 26830879
Mol Ther. 2002 Jun;5(6):788-97
pubmed: 12027564
J Clin Invest. 2016 Jul 1;126(7):2745-56
pubmed: 27322062
Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6626-33
pubmed: 23542380
AIDS. 2010 Jun 19;24(10):1598-601
pubmed: 20549847
Curr Opin HIV AIDS. 2019 Mar;14(2):100-107
pubmed: 30601239
Sex Transm Infect. 2017 Jul;93(Suppl 3):
pubmed: 28736390
PLoS Pathog. 2018 Nov 1;14(11):e1007222
pubmed: 30383857
Science. 1999 Jul 30;285(5428):727-9
pubmed: 10426993
Open AIDS J. 2016 Apr 08;10:34-48
pubmed: 27347270
Curr Opin HIV AIDS. 2019 Jul;14(4):318-324
pubmed: 31082819
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16934-9
pubmed: 20837531
Science. 2011 Sep 16;333(6049):1633-7
pubmed: 21764753
J Infect Dis. 2010 Nov 15;202(10):1553-61
pubmed: 20939732
Immunity. 2016 Jul 19;45(1):31-45
pubmed: 27438765
J Biol Chem. 2001 Mar 2;276(9):6591-604
pubmed: 11096108
Pharmacology. 2017;100(5-6):229-242
pubmed: 28743107
J Clin Oncol. 2019 Feb 1;37(4):328-335
pubmed: 30557517
Cell Host Microbe. 2015 Sep 9;18(3):345-53
pubmed: 26355217
PLoS One. 2010 Jun 16;5(6):e11160
pubmed: 20585398
PLoS Pathog. 2013 Mar;9(3):e1003211
pubmed: 23516360
PLoS Med. 2017 Nov 14;14(11):e1002435
pubmed: 29136037
Am J Cancer Res. 2016 Jan 15;6(2):403-24
pubmed: 27186412
Int J Mol Sci. 2019 Apr 12;20(8):
pubmed: 31013813
Antivir Chem Chemother. 2014 Jan 29;23(4):145-9
pubmed: 24318952
Nature. 2015 Jan 15;517(7534):381-5
pubmed: 25561180
Drug Discov Today. 2018 Jun;23(6):1175-1182
pubmed: 29501911
Curr Opin Immunol. 2007 Aug;19(4):408-15
pubmed: 17656078
Blood. 2012 Mar 22;119(12):2709-20
pubmed: 22160384
J Infect Dis. 1999 Dec;180(6):1827-32
pubmed: 10558937
Nature. 2012 Jul 25;487(7408):482-5
pubmed: 22837004
Sci Transl Med. 2013 Dec 11;5(215):215ra172
pubmed: 24337479
PLoS Pathog. 2010 May 27;6(5):e1000917
pubmed: 20523897
J Virol. 2002 Feb;76(4):1626-31
pubmed: 11799157
BioDrugs. 2017 Dec;31(6):473-481
pubmed: 29143249
Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):E3268-77
pubmed: 23115339
J Clin Invest. 2016 Feb;126(2):455-63
pubmed: 26731469
Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552-7
pubmed: 18490657
Nat Med. 1995 Dec;1(12):1284-90
pubmed: 7489410
Cell. 2007 Nov 30;131(5):861-72
pubmed: 18035408
AIDS. 1999 Dec 3;13(17):2405-10
pubmed: 10597782
J Virol. 2018 Sep 12;92(19):
pubmed: 29997203
J Infect Dis. 2003 May 15;187(10):1534-43
pubmed: 12721933
Nat Med. 2018 Nov;24(11):1701-1707
pubmed: 30258217
Nature. 2018 Nov;563(7731):360-364
pubmed: 30283138
Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4204-9
pubmed: 15010526
Immunogenetics. 2001 May-Jun;53(4):279-87
pubmed: 11491531
Clin Cancer Res. 2017 May 1;23(9):2255-2266
pubmed: 27815355
J Natl Cancer Inst. 2019 Jul 1;111(7):719-726
pubmed: 30551196
FASEB J. 2013 Jun;27(6):2440-50
pubmed: 23395909
Nat Med. 1999 Jun;5(6):651-5
pubmed: 10371503
Nat Biotechnol. 2013 Oct;31(10):928-33
pubmed: 23934177
J Clin Invest. 2018 Mar 1;128(3):1190-1198
pubmed: 29457784
Cell Stem Cell. 2019 Apr 4;24(4):566-578.e7
pubmed: 30853558
Science. 1996 Nov 8;274(5289):985-9
pubmed: 8875941
J Exp Med. 2010 Mar 15;207(3):521-34
pubmed: 20212069
J Virol. 2013 Jun;87(11):6521-5
pubmed: 23536672
J Clin Invest. 2015 May;125(5):1901-12
pubmed: 25822022
Nature. 2011 Sep 22;477(7365):466-70
pubmed: 21849977
AIDS Res Hum Retroviruses. 2019 Jan;35(1):1-24
pubmed: 30351168
J Infect Dis. 2008 Mar 1;197(5):714-20
pubmed: 18260759
Science. 2009 Mar 6;323(5919):1304-7
pubmed: 19265012
Stem Cell Rev Rep. 2019 Jun;15(3):443-447
pubmed: 30826931
Curr Opin HIV AIDS. 2016 Jul;11(4):394-401
pubmed: 26974532