Engineered cell-based therapies in ex vivo ready-made CellDex capsules have therapeutic efficacy in solid tumors - 29/04/23
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.
Le texte complet de cet article est disponible en 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. |
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
Plan
Vol 162
Article 114665- juin 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?