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
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.
引用
收藏
页码:596 / +
页数:26
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