Back to Search Start Over

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

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

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
Source :
Nature Communications, Vol 13, Iss 1, Pp 1-16 (2022)
Publication Year :
2022
Publisher :
Nature Portfolio, 2022.

Abstract

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.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
13
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.3728edd112e43e6baeb95ff129c6000
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-022-30558-3