Anti-TACI single and dual-targeting CAR T cells overcome BCMA antigen loss in multiple myeloma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 Nov 2023
18 Nov 2023
Historique:
received:
18
08
2023
accepted:
09
11
2023
medline:
27
11
2023
pubmed:
19
11
2023
entrez:
18
11
2023
Statut:
epublish
Résumé
Chimeric Antigen Receptor (CAR) T cells directed to B cell maturation antigen (BCMA) mediate profound responses in patients with multiple myeloma, but most patients do not achieve long-term complete remissions. In addition, recent evidence suggests that high-affinity binding to BCMA can result in on-target, off-tumor activity in the basal ganglia and can lead to fatal Parkinsonian-like disease. Here we develop CAR T cells against multiple myeloma using a binder to targeting transmembrane activator and CAML interactor (TACI) in mono and dual-specific formats with anti-BCMA. These CARs have robust, antigen-specific activity in vitro and in vivo. We also show that TACI RNA expression is limited in the basal ganglia, which may circumvent some of the toxicities recently reported with BCMA CARs. Thus, single-targeting TACI CARs may have a safer toxicity profile, whereas dual-specific BCMA-TACI CAR T cells have potential to avoid the antigen escape that can occur with single-antigen targeting.
Identifiants
pubmed: 37980341
doi: 10.1038/s41467-023-43416-7
pii: 10.1038/s41467-023-43416-7
pmc: PMC10657357
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
B-Cell Maturation Antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7509Subventions
Organisme : NCI NIH HHS
ID : R01 CA238268
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA249062
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA252940
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007529
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Gene Ther. 2021 Sep;28(9):560-571
pubmed: 33846552
Mayo Clin Proc. 2017 Apr;92(4):578-598
pubmed: 28291589
Clin Cancer Res. 2013 Apr 15;19(8):2048-60
pubmed: 23344265
Nat Med. 2021 Apr;27(4):616-619
pubmed: 33619368
J Clin Oncol. 2018 Aug 1;36(22):2267-2280
pubmed: 29812997
Nat Med. 2021 Dec;27(12):2099-2103
pubmed: 34893771
Blood. 2016 May 19;127(20):2406-10
pubmed: 26907630
Mol Brain. 2014 Nov 18;7:83
pubmed: 25406675
Cancer Discov. 2015 Dec;5(12):1282-95
pubmed: 26516065
Lancet. 2021 Jul 24;398(10297):314-324
pubmed: 34175021
Leukemia. 2019 Jan;33(1):159-170
pubmed: 29967379
J Immunother Cancer. 2023 Jun;11(6):
pubmed: 37399355
Am J Hematol. 2016 Jul;91(7):719-34
pubmed: 27291302
Cell Mol Immunol. 2017 Aug;14(8):662-674
pubmed: 28626234
Nat Rev Drug Discov. 2021 May;20(5):332
pubmed: 33790473
Nat Immunol. 2001 Jul;2(7):632-7
pubmed: 11429548
N Engl J Med. 2021 Feb 25;384(8):705-716
pubmed: 33626253
Blood Adv. 2019 Nov 12;3(21):3248-3260
pubmed: 31698455
Clin Lymphoma Myeloma Leuk. 2015 Nov;15(11):687-93
pubmed: 26361647
J Immunother Cancer. 2022 Nov;10(11):
pubmed: 36323436
Crit Rev Immunol. 2012;32(4):287-305
pubmed: 23237506
Nat Med. 2018 Jan;24(1):20-28
pubmed: 29155426
Nature. 2012 Sep 20;489(7416):391-399
pubmed: 22996553
Blood. 2018 Feb 15;131(7):746-758
pubmed: 29284597
Ann Oncol. 2017 Jul 1;28(suppl_4):iv52-iv61
pubmed: 28453614
Nat Commun. 2021 Feb 8;12(1):868
pubmed: 33558511
J Natl Compr Canc Netw. 2018 Jan;16(1):11-20
pubmed: 29295877
Sci Transl Med. 2019 Mar 27;11(485):
pubmed: 30918115
Blood. 2017 Dec 28;130(26):2838-2847
pubmed: 29089311
N Engl J Med. 2022 Sep 29;387(13):1196-1206
pubmed: 36170501
Leukemia. 2019 Feb;33(2):426-438
pubmed: 30135465
Blood Cancer J. 2022 Feb 24;12(2):32
pubmed: 35210399
Blood. 2004 Jan 15;103(2):689-94
pubmed: 14512299
N Engl J Med. 2019 May 2;380(18):1726-1737
pubmed: 31042825
Br J Haematol. 2015 Oct;171(2):205-209
pubmed: 26084925
Cancer Immunol Res. 2016 Jun;4(6):498-508
pubmed: 27059623
Mol Cell Proteomics. 2023 Jan;22(1):100452
pubmed: 36423813
Clin Cancer Res. 2019 Dec 1;25(23):7046-7057
pubmed: 31439577