Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting

被引：122

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：

CANCER CELL | 2018年 / 34卷 / 04期

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

页码：596 / +

页数：26

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