Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids

Chimeric antigen receptor (CAR-) T cells are revolutionizing cancer treatment, as a direct result of their clinical impact on the treatment of hematological malignancies. However for solid tumors, CAR-T cell therapeutic efficacy remains limited, primarily due to the complex immunosuppressive tumor m...

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Autores principales: Suraiya, Anisha B., Evtimov, Vera J., Truong, Vinh X., Boyd, Richard L., Forsythe, John S., Boyd, Nicholas R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334344/
https://www.ncbi.nlm.nih.gov/pubmed/35905640
http://dx.doi.org/10.1016/j.tranon.2022.101477
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author Suraiya, Anisha B.
Evtimov, Vera J.
Truong, Vinh X.
Boyd, Richard L.
Forsythe, John S.
Boyd, Nicholas R.
author_facet Suraiya, Anisha B.
Evtimov, Vera J.
Truong, Vinh X.
Boyd, Richard L.
Forsythe, John S.
Boyd, Nicholas R.
author_sort Suraiya, Anisha B.
collection PubMed
description Chimeric antigen receptor (CAR-) T cells are revolutionizing cancer treatment, as a direct result of their clinical impact on the treatment of hematological malignancies. However for solid tumors, CAR-T cell therapeutic efficacy remains limited, primarily due to the complex immunosuppressive tumor microenvironment, inefficient access to tumor cells and poor persistence of the killer cells. In this in vitro study, an injectable, gelatin-based micro-hydrogel system that can encapsulate and deliver effective CAR-T therapy is investigated. CAR-T cells targeting TAG-72, encapsulated in these microgels possessed high viability (> 87%) after 7 days, equivalent to those grown under normal expansion conditions, with retention of the T cell phenotype and functionality. Microgel recovered CAR-T cells demonstrated potent on-target cytotoxicity against human ovarian cancer in vitro and on three-dimensional tumor spheroids, by completely eliminating tumor cells. The gelatin-based micro-hydrogels have the potential to serve as carrier systems to augment CAR-T immunotherapeutic treatment of solid tumors.
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spelling pubmed-93343442022-08-01 Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids Suraiya, Anisha B. Evtimov, Vera J. Truong, Vinh X. Boyd, Richard L. Forsythe, John S. Boyd, Nicholas R. Transl Oncol Perspective Chimeric antigen receptor (CAR-) T cells are revolutionizing cancer treatment, as a direct result of their clinical impact on the treatment of hematological malignancies. However for solid tumors, CAR-T cell therapeutic efficacy remains limited, primarily due to the complex immunosuppressive tumor microenvironment, inefficient access to tumor cells and poor persistence of the killer cells. In this in vitro study, an injectable, gelatin-based micro-hydrogel system that can encapsulate and deliver effective CAR-T therapy is investigated. CAR-T cells targeting TAG-72, encapsulated in these microgels possessed high viability (> 87%) after 7 days, equivalent to those grown under normal expansion conditions, with retention of the T cell phenotype and functionality. Microgel recovered CAR-T cells demonstrated potent on-target cytotoxicity against human ovarian cancer in vitro and on three-dimensional tumor spheroids, by completely eliminating tumor cells. The gelatin-based micro-hydrogels have the potential to serve as carrier systems to augment CAR-T immunotherapeutic treatment of solid tumors. Neoplasia Press 2022-07-26 /pmc/articles/PMC9334344/ /pubmed/35905640 http://dx.doi.org/10.1016/j.tranon.2022.101477 Text en © 2022 Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Perspective
Suraiya, Anisha B.
Evtimov, Vera J.
Truong, Vinh X.
Boyd, Richard L.
Forsythe, John S.
Boyd, Nicholas R.
Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids
title Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids
title_full Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids
title_fullStr Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids
title_full_unstemmed Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids
title_short Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids
title_sort micro-hydrogel injectables that deliver effective car-t immunotherapy against 3d solid tumor spheroids
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334344/
https://www.ncbi.nlm.nih.gov/pubmed/35905640
http://dx.doi.org/10.1016/j.tranon.2022.101477
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