CTNI-30. MESENCHYMAL STEM CELL (MSC11FCD) BASED THERAPY ELICITED A FAVORABLE RESPONSE WITH EFFICIENT 5-FU CONVERSION IN PATIENTS WITH RECURRENT GLIOBLASTOMA: AN OPEN LABEL, PHASE I/IIA TRIAL

Abstract

Abstract Mesenchymal stem cells (MSC) are being developed as therapeutic agents for treatment of various diseases due to their high tropism to damaged sites and cancers, and low immunogenicity. We are developing technologies to efficiently transfer therapeutic genes including suicide genes that will be used to suppress tumor growth or to ensure safety against possible adverse events and to develop off-the-shelf formulations for allogeneic uses. MSCs were engineered to express a suicide gene encoding non-human cytosine deaminase (CD) enzymes. We aimed to conduct a phase I/IIa clinical trial to investigate the maximum tolerated dose, safety, and efficiency of MSC11FCD in recurrent glioblastoma (GBM) patients. This study was a single-arm, open label, investigator-initiated trial on 10 patients recruited between 2021. The MSCs were administered via intra-tumoral injection after surgical resection. No severe adverse events and dose-dependent toxicities were observed. Median overall survival was not reached, and the median progression-free survival was over 4 months. We identified efficient 5-FU production and specific gene signature as biomarkers that predict response to MSC11FCD therapeutics in recurrent GBM, which might provide a new treatment strategy for this highly aggressive tumor. In conclusion, MSC11FCD therapy was safe and showed clinical efficiency in recurrent GBM patients. Specific gene signature can be used to screen individuals who might benefit from MSC11FCD therapy.