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 ShahPublished 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.
Keyphrases
- end stage renal disease
- stem cells
- positron emission tomography
- circulating tumor cells
- mesenchymal stem cells
- chronic kidney disease
- ejection fraction
- clinical trial
- pet imaging
- newly diagnosed
- prognostic factors
- stem cell transplantation
- peritoneal dialysis
- drug delivery
- bone marrow
- metabolic syndrome
- adipose tissue
- autism spectrum disorder
- intellectual disability
- binding protein
- patient reported
- open label
- highly efficient
- editorial comment
- pet ct