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

Deepak BhereSung Hugh ChoiPim van de DonkDavid L HopeKiki GortzakAmina KunnummalJasneet KhalsaEsther Revai-LechtichClemens ReinshagenVictoria LeonNabil NissarWenya Linda BiCheng FengHongbin LiYu Shrike ZhangSteven H LiangNeil VasdevWalid Ibn EssayedPablo Valdes QuevedoAlexandra GolbyNaima BanouniAnna PalaginaReza AbdiBrian FuryStelios Manolis SmirnakisAlarice LoweBrock ReeveArthur HillerE Antonio ChioccaGlenn PrestwichHiroaki WakimotoGerhard BauerKhalid Shah
Published in: Nature communications (2022)
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.
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