RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-30558-3 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Deepak Bhere |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c3728edd112e43e6baeb95ff129c6000 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c3728edd112e43e6baeb95ff129c60002025-08-20T03:41:47ZengNature PortfolioNature Communications2041-17232022-05-0113111610.1038/s41467-022-30558-3RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cellsDeepak Bhere0Sung Hugh Choi1Pim van de Donk2David Hope3Kiki Gortzak4Amina Kunnummal5Jasneet Khalsa6Esther Revai Lechtich7Clemens Reinshagen8Victoria Leon9Nabil Nissar10Wenya Linda Bi11Cheng Feng12Hongbin Li13Yu Shrike Zhang14Steven H. Liang15Neil Vasdev16Walid Ibn Essayed17Pablo Valdes Quevedo18Alexandra Golby19Naima Banouni20Anna Palagina21Reza Abdi22Brian Fury23Stelios Smirnakis24Alarice Lowe25Brock Reeve26Arthur Hiller27E. Antonio Chiocca28Glenn Prestwich29Hiroaki Wakimoto30Gerhard Bauer31Khalid Shah32Center for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolUC Davis Institute for Regenerative CuresDepartment of Neurology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical SchoolHarvard Stem Cell Institute, Harvard UniversityAmasa Therapeutics Inc.Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Medicinal Chemistry, College of Pharmacy University of UtahCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolUC Davis Institute for Regenerative CuresCenter for Stem Cell and Translational Immunotherapy (CSTI), Brigham and Women’s Hospital, Harvard Medical SchoolAbstract 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.https://doi.org/10.1038/s41467-022-30558-3 |
| spellingShingle | 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 RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells Nature Communications |
| title | RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells |
| title_full | RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells |
| title_fullStr | RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells |
| title_full_unstemmed | RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells |
| title_short | RETRACTED ARTICLE: Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells |
| title_sort | retracted article target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells |
| url | https://doi.org/10.1038/s41467-022-30558-3 |
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