Universität zu Köln

Hombach, Andreas A., Geumann, Ulf, Guenther, 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). BASEL: MDPI. ISSN 2073-4409

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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 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hombach, Andreas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Geumann, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenther, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hermann, Felix G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-338252
DOI:	10.3390/cells9040873
Journal or Publication Title:	Cells
Volume:	9
Number:	4
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHIMERIC ANTIGEN RECEPTORS; SINGLE-CHAIN ANTIBODY; GENETIC-MODIFICATION; CD28 COSTIMULATION; STROMAL CELLS; SPACER DOMAIN; DELIVERY; THERAPY; ACTIVATION; TRAIL Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33825