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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2022
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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. |
format | Online Article Text |
id | pubmed-9334344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
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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