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IL7-IL12 Engineered Mesenchymal Stem Cells (MSCs) Improve A CAR T Cell Attack Against Colorectal Cancer Cells
Hombach, Andreas A., Geumann, Ulf, Günther, Christine, Hermann, Felix G. and Abken, Hinrich (2020) IL7-IL12 Engineered Mesenchymal Stem Cells (MSCs) Improve A CAR T Cell Attack Against Colorectal Cancer Cells. Cells 9 (4), p. 873.Date of publication of this fulltext: 08 Apr 2020 10:13
Article
DOI to cite this document: 10.5283/epub.43047
Abstract
Chimeric antigen receptor (CAR) redirected T cells are efficacious in the treatment of leukemia/lymphoma, however, showed less capacities in eliminating solid tumors which is thought to be partly due to the lack of cytokine support in the tumor lesion. In order to deliver supportive cytokines, we took advantage of the inherent ability of mesenchymal stem cells (MSCs) to actively migrate to tumor ...
Chimeric antigen receptor (CAR) redirected T cells are efficacious in the treatment of leukemia/lymphoma, however, showed less capacities in eliminating solid tumors which is thought to be partly due to the lack of cytokine support in the tumor lesion. In order to deliver supportive cytokines, we took advantage of the inherent ability of mesenchymal stem cells (MSCs) to actively migrate to tumor sites and engineered MSCs to release both IL7 and IL12 to promote homeostatic expansion and Th1 polarization. There is a mutual interaction between engineered MSCs and CAR T cells; in presence of CAR T cell released IFN-gamma and TNF-alpha, chronic inflammatory Th2 MSCs shifted towards a Th17/Th1 pattern with IL2 and IL15 release that mutually activated CAR T cells with extended persistence, amplification, killing and protection from activation induced cell death. MSCs releasing IL7 and IL12 were superior over non-modified MSCs in supporting the CAR T cell response and improved the anti-tumor attack in a transplant tumor model. Data demonstrate the first use of genetically modified MSCs as vehicles to deliver immuno-modulatory proteins to the tumor tissue in order to improve the efficacy of CAR T cells in the treatment of solid malignancies.
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Details
| Item type | Article | ||||
| Journal or Publication Title | Cells | ||||
| Publisher: | MDPI | ||||
|---|---|---|---|---|---|
| Place of Publication: | BASEL | ||||
| Volume: | 9 | ||||
| Number of Issue or Book Chapter: | 4 | ||||
| Page Range: | p. 873 | ||||
| Date | 3 April 2020 | ||||
| Institutions | Leibniz Institute for Immunotherapy (LIT) | ||||
| Identification Number |
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| Keywords | CHIMERIC ANTIGEN RECEPTORS; SINGLE-CHAIN ANTIBODY; GENETIC-MODIFICATION; CD28 COSTIMULATION; STROMAL CELLS; SPACER DOMAIN; DELIVERY; THERAPY; ACTIVATION; TRAIL; CAR T cells; MSC; adoptive cell therapy; genetic immunotherapy; IL7; IL12 | ||||
| Dewey Decimal Classification | 600 Technology > 610 Medical sciences Medicine | ||||
| Status | Published | ||||
| Refereed | Yes, this version has been refereed | ||||
| Created at the University of Regensburg | Yes | ||||
| URN of the UB Regensburg | urn:nbn:de:bvb:355-epub-430479 | ||||
| Item ID | 43047 |
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