CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
25 09 2019
25 09 2019
Historique:
received:
07
02
2019
revised:
03
04
2019
accepted:
31
07
2019
entrez:
27
9
2019
pubmed:
27
9
2019
medline:
21
8
2020
Statut:
ppublish
Résumé
CAR T cells targeting CD19 provide promising options for treatment of B cell malignancies. However, tumor relapse from antigen loss can limit efficacy. We developed humanized, second-generation CAR T cells against another B cell-specific marker, B cell activating factor receptor (BAFF-R), which demonstrated cytotoxicity against human lymphoma and acute lymphoblastic leukemia (ALL) lines. Adoptively transferred BAFF-R-CAR T cells eradicated 10-day preestablished tumor xenografts after a single treatment and retained efficacy against xenografts deficient in CD19 expression, including CD19-negative variants within a background of CD19-positive lymphoma cells. Four relapsed, primary ALLs with CD19 antigen loss obtained after CD19-directed therapy retained BAFF-R expression and activated BAFF-R-CAR, but not CD19-CAR, T cells. BAFF-R-CAR, but not CD19-CAR, T cells also demonstrated antitumor effects against an additional CD19 antigen loss primary patient-derived xenograft (PDX) in vivo. BAFF-R is amenable to CAR T cell therapy, and its targeting may prevent emergence of CD19 antigen loss variants.
Identifiants
pubmed: 31554741
pii: 11/511/eaaw9414
doi: 10.1126/scitranslmed.aaw9414
pmc: PMC7015136
mid: NIHMS1054892
pii:
doi:
Substances chimiques
Antigens, CD19
0
B-Cell Activation Factor Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA213138
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA157644
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA223141
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA137060
Pays : United States
Organisme : Howard Hughes Medical Institute
ID : 55108547
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA233691
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA197498
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180827
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172558
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197628
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA107399
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA236626
Pays : United States
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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