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Injectable Hydrogel for Loco-regional Delivery of CAR-T Cells for Solid Tumor Immunotherapy
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788226
*Corresponding author: (e-mail: prakriti@iitb.ac.in).
Abstract
Background: CAR-T cell therapy has shown remarkable success in hematological malignancies; however, heterogeneity of the solid tumor microenvironment (TME) limits its clinical efficacy. Presence of immunosuppressive cells and a dense extracellular matrix in the TME limit the infiltration of CAR-T cells at the tumor site thereby impeding their functional efficacy.
Materials and Methods: We developed an injectable hydrogel to deliver CAR-T cells locoregionally—to provide direct access to the tumor core. We fabricated a chitosan-based biodegradable, fast-gelling hydrogel which is easily injectable through 21G needle by-passing the need for surgery. The hydrogel was evaluated for physical and biological characterization and in vivo biocompatibility.
Results: Physical characterization of the hydrogel revealed an interconnected and porous matrix—conducive for release of the encapsulated CAR-T cells. It was found to degrade by 20 days in vitro. Furthermore, the hydrogel was cytocompatible, hemocompatible, and supported cellular infiltration. Subcutaneous injection of the hydrogel in immunocompetent mice showed no systemic toxicity. The skin-resident stem cells and T cell population were evaluated and we found no changes in their numbers post-administration of this hydrogel. We evaluated the serum cytokine levels (IL-6, TNF-a, and IFN-y) and observed no change in their profiles—thereby confirming its in vivo biocompatibility.
Conclusion: In summary, we developed a minimally invasive, biocompatible hydrogel that aims to support CAR-T cell viability in the immunosuppressive TME, does not evoke inflammation following injection, and navigates them through solid tumors in a localized manner for better therapeutic outcome.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (e-mail: prakriti@iitb.ac.in).
Abstract
Background: CAR-T cell therapy has shown remarkable success in hematological malignancies; however, heterogeneity of the solid tumor microenvironment (TME) limits its clinical efficacy. Presence of immunosuppressive cells and a dense extracellular matrix in the TME limit the infiltration of CAR-T cells at the tumor site thereby impeding their functional efficacy.
Materials and Methods: We developed an injectable hydrogel to deliver CAR-T cells locoregionally—to provide direct access to the tumor core. We fabricated a chitosan-based biodegradable, fast-gelling hydrogel which is easily injectable through 21G needle by-passing the need for surgery. The hydrogel was evaluated for physical and biological characterization and in vivo biocompatibility.
Results: Physical characterization of the hydrogel revealed an interconnected and porous matrix—conducive for release of the encapsulated CAR-T cells. It was found to degrade by 20 days in vitro. Furthermore, the hydrogel was cytocompatible, hemocompatible, and supported cellular infiltration. Subcutaneous injection of the hydrogel in immunocompetent mice showed no systemic toxicity. The skin-resident stem cells and T cell population were evaluated and we found no changes in their numbers post-administration of this hydrogel. We evaluated the serum cytokine levels (IL-6, TNF-a, and IFN-y) and observed no change in their profiles—thereby confirming its in vivo biocompatibility.
Conclusion: In summary, we developed a minimally invasive, biocompatible hydrogel that aims to support CAR-T cell viability in the immunosuppressive TME, does not evoke inflammation following injection, and navigates them through solid tumors in a localized manner for better therapeutic outcome.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India