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Nat Commun ; 13(1): 2810, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35589724

RESUMO

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 (MSCBif) expressing DR-targeted ligand and a safety kill switch. We show that biodegradable hydrogel encapsulated MSCBif (EnMSCBif) 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 MSCBif 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 EnMSCBif in primary and recurrent GBM patients.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Transplante de Células-Tronco Hematopoéticas , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Humanos , Camundongos , Recidiva Local de Neoplasia/terapia
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