RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells

RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells

Abstract 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...

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Main Authors: Deepak Bhere, Sung Hugh Choi, Pim van de Donk, David Hope, Kiki Gortzak, Amina Kunnummal, Jasneet Khalsa, Esther Revai Lechtich, Clemens Reinshagen, Victoria Leon, Nabil Nissar, Wenya Linda Bi, Cheng Feng, Hongbin Li, Yu Shrike Zhang, Steven H. Liang, Neil Vasdev, Walid Ibn Essayed, Pablo Valdes Quevedo, Alexandra Golby, Naima Banouni, Anna Palagina, Reza Abdi, Brian Fury, Stelios Smirnakis, Alarice Lowe, Brock Reeve, Arthur Hiller, E. Antonio Chiocca, Glenn Prestwich, Hiroaki Wakimoto, Gerhard Bauer, Khalid Shah
Format: Article
Language:English
Published: Nature Portfolio 2022-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-022-30558-3
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Summary:Abstract 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.
ISSN:2041-1723

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