TREATME 1: Treatment of advanced gastrointestinal cancer in a clinical phase I/II trial with genetically modified mesenchymal stem cells: Clinical results of a phase I study

Background: Treatment options based on genetically modified cells may add alternative therapeutic modalites to medical oncology. The investigational medicinal product is a genetically modified mesenchymal-stem-cell-suspension (gmMSC) for i.v. infusion. The integration of the therapeutic gene HerpesSimplexThymidinkinase (HSV-TK) under the control of a tumor specific promoter is accomplished through the use of a SIN-gamma-vector system. Patients received gmMSC -infusion at days 1, 8, 15. Each followed by Ganciclovir (q2d) on day 3-5, 10-12, 17-19. Two dose levels of gmMSC were evaluated. Methods: Six Patients with relapsed gastrointestinal adenocarcinoma and liver and/or lung metastasis non-responsive to standard therapy were treated. No signs of active infection. Dose escalation (1.5 Mio.-to 3.0 Mio. MSC/kg BW) was determined by the German Competent Authority (PEI) after the completion of 3 patients. Patients'- safety/tolerability and technical feasibility of the MSC-acpeth-101 infusion were the main criteria. Results: We report clinical data on a phase I study for the treatment of gastrointestinal adenocarcinoma applying gmMSC. Diagnoses comprised 3 colorectal, 1 cholangiocellular and 2 pancreatic carcinomas. 3/6 patients received low-dose treatment, 3 high-dose treatment. No dose-limitingor off-target toxicities related to the study occured. According to RECIST (1.1) 4/6 showed SD at three months follow-up, 2/6 PD. 1/6 is in sustained SD( > 5 months). Conclusions: This Phase I study demonstrated the feasibility of the protocol and the excellent tolerability of the study-drug. Safety data allow for continuation in phase II with the higher dose level.