Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells

Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by the lack of effective target identification and stringent testing in pre-clinical models that replicate standard treatment in GBM patients. In this study, we show the detection of cell surface death receptor (DR) target on CD146-enriched circulating tumor cells (CTC) captured from the blood of mice bearing GBM and patients diagnosed with GBM. Next, we developed allogeneic “off-the-shelf” clinical-grade bifunctional mesenchymal stem cells (MSC(Bif)) expressing DR-targeted ligand and a safety kill switch. We show that biodegradable hydrogel encapsulated MSC(Bif) (EnMSC(Bif)) has a profound therapeutic efficacy in mice bearing patient-derived invasive, primary and recurrent GBM tumors following surgical resection. Activation of the kill switch enhances the efficacy of MSC(Bif) and results in their elimination post-tumor treatment which can be tracked by positron emission tomography (PET) imaging. This study establishes a foundation towards a clinical trial of EnMSC(Bif) in primary and recurrent GBM patients.