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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. und Abken, Hinrich (2020) IL7-IL12 Engineered Mesenchymal Stem Cells (MSCs) Improve A CAR T Cell Attack Against Colorectal Cancer Cells. Cells 9 (4), S. 873.

Veröffentlichungsdatum dieses Volltextes: 08 Apr 2020 10:13
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.43047


Zusammenfassung

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

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftCells
Verlag:MDPI
Ort der Veröffentlichung:BASEL
Band:9
Nummer des Zeitschriftenheftes oder des Kapitels:4
Seitenbereich:S. 873
Datum3 April 2020
InstitutionenLeibniz-Institut für Immuntherapie (LIT)
Identifikationsnummer
WertTyp
10.3390/cells9040873DOI
Stichwörter / 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-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-430479
Dokumenten-ID43047

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