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

// Jobst C. von Einem 1 , Sylvia Peter 2 , Christine Gunther 2 , Hans-Dieter Volk 3 , Gerald Grutz 3 , Christoph Salat 4 , Oliver Stoetzer 4 , Peter J. Nelson 5 , Marlies Michl 1 , Dominik P. Modest 1 , Julian W. Holch 1 , Martin Angele 6 , Christiane Bruns 7 , Hanno Niess 6,* and Volker Heinemann 1,* 1 Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Grosshadern, LMU, Munich, Germany 2 Apceth GmbH & Co. KG, Munich, Germany 3 Institute for Medical Immunology and Berlin-Brandenburg Center for Regenerative Medicine, Charite-Universitatsmedizin, Berlin, Germany 4 Haemato-Onkologische Schwerpunktpraxis Prof. Salat, Dr. Stoetzer, Munich, Germany 5 Department of Medicine IV, University Hospital of Munich, LMU, Munich, Germany 6 Department of Surgery, University Hospital Grosshadern, LMU, Munich, Germany 7 General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany * These authors have contributed equally to this article Correspondence to: Jobst C. von Einem, email: // Keywords : mesenchymal stem cells, gastrointestinal cancer, CCC, CRC, GDEPT Received : May 10, 2017 Accepted : August 26, 2017 Published : September 16, 2017 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 × 10 6 cells/kg. Two patients received three doses of 1 × 10 6 cells/kg, while one patient received only two doses of 1 × 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.