von Einem, Jobst C., Peter, Sylvia, Guenther, Christine, Volk, Hans-Dieter ORCID: 0000-0002-7743-6668, Guertz, Gerald, Salat, Christoph, Stoetzer, Oliver, Nelson, Peter J., Michl, Marlies, Modest, Dominik P., Holch, Julian W., Angele, Martin, Bruns, Christiane, Niess, Hanno and Heinemann, Volker (2017). Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells - TREAT-ME-1-a phase I, first in human, first in class trial. Oncotarget, 8 (46). S. 80156 - 80167. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Purpose: This phase I, first in human, first in class clinical study aimed at evaluating the safety, tolerability and efficacy of treatment with genetically modified mesenchymal stromal cells (MSC) in combination with ganciclovir (GCV). MSC_apceth_ 101 are genetically modified autologous MSCs used as vehicles for a cell-based gene therapy in patients with advanced gastrointestinal adenocarcinoma. Experimental design: The study design consisted of a dose-escalation 3 + 3 design. All patients (n = 6) were treated with up to three applications of MSC_apceth_101, followed by GCV infusions given on three consecutive days starting 48 hours after injection of MSC_apceth_101. Three of six patients received a total dose of 1.5 x 10(6) cells/kg. Two patients received three doses of 1 x 10(6) cells/kg, while one patient received only two doses of 1 x 10(6) cells/kg due to a SADR. Results: Six patients received MSC_apceth_101. No IMP-related serious adverse events occurred. Adverse-events related to IMP-injection were increased creatinine, cough, fever, and night sweat. TNF, IL-6, IL-8, IL-10 and sE-Selectin, showed that repeated application is immunologically safe, but induces a switch of the functional properties of monocytes to an inflammatory phenotype. Treatment induced stable disease in 4/6 patients, and progressive disease in 2/6 patients. Conclusion: Treatment with MSC_ apceth_101 in combination with GCV demonstrated acceptable safety and tolerability in patients with advanced gastrointestinal adenocarcinoma.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
von Einem, Jobst C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peter, SylviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenther, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volk, Hans-DieterUNSPECIFIEDorcid.org/0000-0002-7743-6668UNSPECIFIED
Guertz, GeraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salat, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoetzer, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nelson, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michl, MarliesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Modest, Dominik P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holch, Julian W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angele, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niess, HannoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinemann, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-214488
DOI: 10.18632/oncotarget.20964
Journal or Publication Title: Oncotarget
Volume: 8
Number: 46
Page Range: S. 80156 - 80167
Date: 2017
Publisher: IMPACT JOURNALS LLC
Place of Publication: ORCHARD PARK
ISSN: 1949-2553
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
STROMAL CELLS; EXPRESSION; DELIVERY; THERAPY; BEVACIZUMAB; SUPPORT; GROWTHMultiple languages
Oncology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21448

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