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Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting
被引:121
|作者:
Rotolo, Antonia
[1
]
Caputo, Valentina S.
[1
]
Holubova, Monika
[1
,2
]
Baxan, Nicoleta
[3
]
Dubois, Olivier
[3
]
Chaudhry, Mohammed Suhail
[1
]
Xiao, Xiaolin
[1
]
Goudevenou, Katerina
[1
]
Pitcher, David S.
[1
]
Petevi, Kyriaki
[1
]
Kachramanoglou, Carolina
[4
]
Iles, Sandra
[5
]
Naresh, Kikkeri
[1
]
Maher, John
[6
]
Karadimitris, Anastasios
[1
]
机构:
[1] Imperial Coll London, Dept Med, Ctr Haematol, London, England
[2] Charles Univ Prague, Med Fac Pilsen, Biomed Ctr, Alej Svobody 76, Plzen 32300, Czech Republic
[3] Imperial Coll London, Dept Med, Biol Imaging Ctr, London, England
[4] Imperial Coll Healthcare NHS Trust, Dept Neuroradiol, London, England
[5] Hammersmith Hosp, Northwest London Pathol, Cellular Pathol, London, England
[6] Kings Coll London, Guys Hosp, Sch Canc & Pharmaceut Sci, London, England
来源:
关键词:
KILLER T-CELLS;
INVARIANT NKT CELLS;
CHRONIC LYMPHOCYTIC-LEUKEMIA;
VERSUS-HOST-DISEASE;
B-CELLS;
ADOPTIVE IMMUNOTHERAPY;
ALPHA-GLYCOSYLCERAMIDE;
DISTINCT SUBSETS;
GENE-EXPRESSION;
RECEPTOR;
D O I:
10.1016/j.ccell.2018.08.017
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19(+) B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1D transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19(+) chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.
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页码:596 / +
页数:26
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