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

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 GolbyNaima 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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Article number2810
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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