Chmielewski, Markus and Abken, Hinrich (2017). CAR T Cells Releasing IL-18 Convert to T-Bet(high) FoxO1(low) Effectors that Exhibit Augmented Activity against Advanced Solid Tumors. Cell Reports, 21 (11). S. 3205 - 3220. CAMBRIDGE: CELL PRESS. ISSN 2211-1247
Full text not available from this repository.Abstract
Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bet high FoxO1 low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines. IL-18 CAR T cell treatment was accompanied by an overall change in the immune cell landscape associated with the tumor. More specifically, CD206(-) M1 macrophages and NKG2D + NK cells increased in number, whereas Tregs, suppressive CD103(+) DCs, and M2 macrophages decreased, suggesting that iIL18 TRUCKs'' can be used to sensitize large solid tumor lesions for successful immune destruction.
Item Type: | Journal Article | ||||||||||||
Creators: |
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URN: | urn:nbn:de:hbz:38-207987 | ||||||||||||
DOI: | 10.1016/j.celrep.2017.11.063 | ||||||||||||
Journal or Publication Title: | Cell Reports | ||||||||||||
Volume: | 21 | ||||||||||||
Number: | 11 | ||||||||||||
Page Range: | S. 3205 - 3220 | ||||||||||||
Date: | 2017 | ||||||||||||
Publisher: | CELL PRESS | ||||||||||||
Place of Publication: | CAMBRIDGE | ||||||||||||
ISSN: | 2211-1247 | ||||||||||||
Language: | English | ||||||||||||
Faculty: | Unspecified | ||||||||||||
Divisions: | Unspecified | ||||||||||||
Subjects: | no entry | ||||||||||||
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Refereed: | Yes | ||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/20798 |
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