RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells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 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 and Khalid Shah ()
Additional contact information
Deepak Bhere: Harvard Medical School
Sung Hugh Choi: Harvard Medical School
Pim van de Donk: Harvard Medical School
David Hope: Harvard Medical School
Kiki Gortzak: Harvard Medical School
Amina Kunnummal: Harvard Medical School
Jasneet Khalsa: Harvard Medical School
Esther Revai Lechtich: Harvard Medical School
Clemens Reinshagen: Harvard Medical School
Victoria Leon: Harvard Medical School
Nabil Nissar: Harvard Medical School
Wenya Linda Bi: Harvard Medical School
Cheng Feng: Harvard Medical School
Hongbin Li: Harvard Medical School
Yu Shrike Zhang: Harvard Medical School
Steven H. Liang: Harvard Medical School
Neil Vasdev: Harvard Medical School
Walid Ibn Essayed: Harvard Medical School
Pablo Valdes Quevedo: Harvard Medical School
Alexandra Golby: Harvard Medical School
Naima Banouni: Harvard Medical School
Anna Palagina: Harvard Medical School
Reza Abdi: Harvard Medical School
Brian Fury: UC Davis Institute for Regenerative Cures
Stelios Smirnakis: Harvard Medical School
Alarice Lowe: Harvard Medical School
Brock Reeve: Harvard University
Arthur Hiller: Amasa Therapeutics Inc.
E. Antonio Chiocca: Harvard Medical School
Glenn Prestwich: College of Pharmacy University of Utah
Hiroaki Wakimoto: Harvard Medical School
Gerhard Bauer: UC Davis Institute for Regenerative Cures
Khalid Shah: Harvard Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-16

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.

Date: 2022
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DOI: 10.1038/s41467-022-30558-3

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