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Hombach, Andreas A. ; Geumann, Ulf ; Günther, Christine ; Hermann, Felix G. ; Abken, Hinrich

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.



Involved Institutions


Details

Item typeArticle
Journal or Publication TitleCells
Publisher:MDPI
Place of Publication:BASEL
Volume:9
Number of Issue or Book Chapter:4
Page Range:p. 873
Date3 April 2020
InstitutionsLeibniz Institute for Immunotherapy (LIT)
Identification Number
ValueType
10.3390/cells9040873DOI
KeywordsCHIMERIC 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 Classification600 Technology > 610 Medical sciences Medicine
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgYes
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-430479
Item ID43047

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