Bispecific CD33/CD123 targeted chimeric antigen receptor T cells for the treatment of acute myeloid leukemia.
AML
CAR T
CD123
CD33
immunotherapy
“AND” logic gate
Journal
Molecular therapy oncolytics
ISSN: 2372-7705
Titre abrégé: Mol Ther Oncolytics
Pays: United States
ID NLM: 101666776
Informations de publication
Date de publication:
19 Dec 2023
19 Dec 2023
Historique:
received:
06
10
2022
accepted:
16
11
2023
medline:
11
12
2023
pubmed:
11
12
2023
entrez:
11
12
2023
Statut:
epublish
Résumé
CD33 and CD123 are expressed on the surface of human acute myeloid leukemia blasts and other noncancerous tissues such as hematopoietic stem cells. On-target off-tumor toxicities may limit chimeric antigen receptor T cell therapies that target both CD33 and CD123. To overcome this limitation, we developed bispecific human CD33/CD123 chimeric antigen receptor (CAR) T cells with an "AND" logic gate. We produced novel CD33 and CD123 scFvs from monoclonal antibodies that bound CD33 and CD123 and activated T cells. Screening of CD33 and CD123 CAR T cells for cytotoxicity, cytokine production, and proliferation was performed, and we selected scFvs for CD33/CD123 bispecific CARs. The bispecific CARs split 4-1BB co-stimulation on one scFv and CD3ζ on the other.
Identifiants
pubmed: 38075241
doi: 10.1016/j.omto.2023.100751
pii: S2372-7705(23)00100-6
pmc: PMC10701585
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100751Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
M.L.D. has received research funding from Novartis, Kite/Gilead, and CRISPR. M.L.D. receives fees from Synthekine, Adicet, Bellicum, Capistan, and Syncopation. M.L.D. has stock or stock options with Adaptive Biotechnologies, Adicet, and Bellicum. M.L.D. has licensed inventions to CRISPR and Atara. M.L.D. has patents related to the CAR described.
Références
Leukemia. 2000 Oct;14(10):1777-84
pubmed: 11021753
N Engl J Med. 2017 Nov 30;377(22):2167-2179
pubmed: 29171820
N Engl J Med. 2014 Oct 16;371(16):1507-17
pubmed: 25317870
Haematologica. 2015 Mar;100(3):336-44
pubmed: 25480499
J Immunother Cancer. 2021 Sep;9(9):
pubmed: 34531250
PLoS One. 2013 Apr 09;8(4):e61338
pubmed: 23585892
Br J Haematol. 2002 Aug;118(2):385-400
pubmed: 12139722
Cancer Cell. 2017 Oct 9;32(4):506-519.e5
pubmed: 29017060
Leukemia. 2015 Aug;29(8):1637-47
pubmed: 25721896
N Engl J Med. 2020 Apr 2;382(14):1331-1342
pubmed: 32242358
Cell. 2018 May 31;173(6):1439-1453.e19
pubmed: 29856956
Leukemia. 2018 Jun;32(6):1317-1326
pubmed: 29515236
Leukemia. 2019 Jan;33(1):64-74
pubmed: 29946192
Sci Transl Med. 2014 Feb 19;6(224):224ra25
pubmed: 24553386
N Engl J Med. 1988 Dec 22;319(25):1676-80
pubmed: 3264384
Nat Rev Immunol. 2002 Feb;2(2):85-95
pubmed: 11910899
Blood. 2014 Jul 17;124(3):363-73
pubmed: 24914140
Cancer Immunol Res. 2013 Jul;1(1):43-53
pubmed: 24409448
Nat Rev Clin Oncol. 2012 Oct;9(10):579-90
pubmed: 22949046
Blood Cancer J. 2014 Jun 13;4:e218
pubmed: 24927407
Cell. 2016 Oct 6;167(2):419-432.e16
pubmed: 27693353
Sci Transl Med. 2012 Aug 29;4(149):149ra118
pubmed: 22932223
Mol Ther. 2017 Sep 6;25(9):2189-2201
pubmed: 28676342
Blood. 2014 Apr 10;123(15):2343-54
pubmed: 24596416
Nat Rev Clin Oncol. 2016 Jun;13(6):370-83
pubmed: 27000958
Proc Natl Acad Sci U S A. 2019 Jun 11;116(24):11978-11987
pubmed: 31138698
J Clin Med. 2019 Feb 06;8(2):
pubmed: 30736352
Leuk Res. 2022 Oct;121:106928
pubmed: 35963025
Haematologica. 2019 Jul;104(7):1302-1308
pubmed: 31221785
JCI Insight. 2018 Sep 20;3(18):
pubmed: 30232281
J Immunother. 2020 Apr;43(3):79-88
pubmed: 31834208
Nat Commun. 2021 Nov 8;12(1):6436
pubmed: 34750374
Nat Biotechnol. 2013 Jan;31(1):71-5
pubmed: 23242161
Methods Mol Biol. 2017;1514:111-118
pubmed: 27787796
Nature. 2014 Feb 20;506(7488):328-33
pubmed: 24522528
Leukemia. 2021 Nov;35(11):3282-3286
pubmed: 33833386
Leukemia. 2014 Aug;28(8):1596-605
pubmed: 24504024
Sci Signal. 2020 Mar 31;13(625):
pubmed: 32234960
Mol Ther. 2015 Jan;23(1):184-91
pubmed: 25174587
Am J Obstet Gynecol. 1997 Sep;177(3):619-25
pubmed: 9322633
Haematologica. 2001 Dec;86(12):1261-9
pubmed: 11726317
J Exp Med. 1997 Jul 7;186(1):47-55
pubmed: 9206996
Leuk Res. 1984;8(4):521-34
pubmed: 6590930
Br J Haematol. 2008 Dec;143(5):744-6
pubmed: 19036018
Cancer Discov. 2020 May;10(5):702-723
pubmed: 32193224
Science. 2006 Oct 6;314(5796):126-9
pubmed: 16946036
Eur J Haematol. 1989 Feb;42(2):143-9
pubmed: 2465178
Blood. 2021 Nov 11;138(19):1830-1842
pubmed: 34289026
PLoS One. 2016 Aug 22;11(8):e0159477
pubmed: 27548616
J Clin Immunol. 2012 Oct;32(5):1059-70
pubmed: 22526592
Nat Rev Clin Oncol. 2020 Mar;17(3):147-167
pubmed: 31848460
N Engl J Med. 2017 Dec 28;377(26):2531-2544
pubmed: 29226797