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Engineered cell-based therapies in ex vivo ready-made CellDex capsules have therapeutic efficacy in solid tumors - 29/04/23

Doi : 10.1016/j.biopha.2023.114665 
Thijs A. van Schaik a, b, Lucia Moreno-Lama a, b, Touraj Aligholipour Farzani a, b, Mian Wang c, Kok-Siong Chen a, b, Wanlu Li c, Ling Cai c, Yu Shrike Zhang c, Khalid Shah a, b, d,
a Center for Stem Cell and Translational Immunotherapy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA 
b Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA 
c Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA 
d Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA 

Correspondence to: Center for Stem Cell and Translational Immunotherapy, Brigham and Women’s Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, íUSA.Center for Stem Cell and Translational Immunotherapy, Brigham and Women’s Hospital, Harvard Medical School60 Fenwood RoadBostonMA02115USA

Abstract

Encapsulated cell-based therapies for solid tumors have shown promising results in pre-clinical settings. However, the inability to culture encapsulated therapeutic cells prior to their transplantation has limited their translation into clinical settings. In this study, we created a wide variety of engineered therapeutic cells (ThC) loaded in micropore-forming gelatin methacryloyl (GelMA) hydrogel (CellDex) capsules that can be cultured in vitro prior to their transplantation in surgically debulked solid tumors. We show that both allogeneic and autologous engineered cells, such as stem cells (SCs), macrophages, NK cells, and T cells, proliferate within CellDex capsules and migrate out of the gel in vitro and in vivo. Furthermore, tumor cell specific therapeutic proteins and oncolytic viruses released from CellDex capsules retain and prolong their anti-tumor effects. In vivo, ThCs in pre-manufactured Celldex capsules persist long-term and track tumor cells. Moreover, chimeric antigen receptor (CAR) T cell bearing CellDex (T-CellDex) and human SC releasing therapeutic proteins (hSC-CellDex) capsules show therapeutic efficacy in metastatic and primary brain tumor resection models that mimic standard of care of tumor resection in patients. Overall, this unique approach of pre-manufactured micropore-forming CellDex capsules offers an effective off-the-shelf clinically viable strategy to treat solid tumors locally.

Il testo completo di questo articolo è disponibile in PDF.

Highlights

CellDex capsules are a next generation of “off the shelf” cell-based cancer therapies.
A wide variety of therapeutic cells persist in CellDex capsules in vivo.
Homing and anti-tumor effects of therapeutic cells are retained in CellDex capsules in vivo.
CellDex capsules have therapeutic efficacy after transplantation in post-surgical tumor resection cavities.

Il testo completo di questo articolo è disponibile in PDF.

Abbreviations : ThC, GelMA, CAR, SC, NK cell, Mac, TME, HA, PEG, BLI, Fluc, mC, FmC, BBM, GBM, MMP

Keywords : Cell-based therapies, Gel encapsulation, 3D bioprinting, Surgical tumor resection, Molecular engineering, Cancer immunotherapy


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© 2023  The Authors. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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Articolo 114665- giugno 2023 Ritorno al numero
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