Nature Communications (May 2022)
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,
- Khalid Shah
Affiliations
- Deepak Bhere
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Sung Hugh Choi
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Pim van de Donk
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- David Hope
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Kiki Gortzak
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Amina Kunnummal
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Jasneet Khalsa
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Esther Revai Lechtich
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Clemens Reinshagen
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Victoria Leon
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Nabil Nissar
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Wenya Linda Bi
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
- Cheng Feng
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
- Hongbin Li
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
- Yu Shrike Zhang
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
- Steven H. Liang
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School
- Neil Vasdev
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School
- Walid Ibn Essayed
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
- Pablo Valdes Quevedo
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
- Alexandra Golby
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
- Naima Banouni
- Department of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School
- Anna Palagina
- Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School
- Reza Abdi
- Department of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School
- Brian Fury
- UC Davis Institute for Regenerative Cures
- Stelios Smirnakis
- Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School
- Alarice Lowe
- Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School
- Brock Reeve
- Harvard Stem Cell Institute, Harvard University
- Arthur Hiller
- Amasa Therapeutics Inc.
- E. Antonio Chiocca
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
- Glenn Prestwich
- Department of Medicinal Chemistry, College of Pharmacy University of Utah
- Hiroaki Wakimoto
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- Gerhard Bauer
- UC Davis Institute for Regenerative Cures
- Khalid Shah
- Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical School
- DOI
- https://doi.org/10.1038/s41467-022-30558-3
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 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.
