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CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B
(1) Background: The lack of specific targets has slowed the progress of CAR-T in treating solid tumors. Recent studies have revealed that EDB-FN (fibronectin extra domain B) may be an effective target for CAR-T treatment of solid tumors; EDB-FN is expressed in tumor and embryonic tissues, and antibo...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496916/ https://www.ncbi.nlm.nih.gov/pubmed/36139437 http://dx.doi.org/10.3390/cells11182863 |
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author | Zhang, Zhijie Liu, Chang Yang, Zhe Yin, Hongping |
author_facet | Zhang, Zhijie Liu, Chang Yang, Zhe Yin, Hongping |
author_sort | Zhang, Zhijie |
collection | PubMed |
description | (1) Background: The lack of specific targets has slowed the progress of CAR-T in treating solid tumors. Recent studies have revealed that EDB-FN (fibronectin extra domain B) may be an effective target for CAR-T treatment of solid tumors; EDB-FN is expressed in tumor and embryonic tissues, and antibody–cytokine fusion proteins targeting EDB-FN have been developed. However, the therapeutic effects of BBz CAR-engineered T-cells targeting EDB-FN in solid tumors have not been evaluated. (2) Results: In this study, we constructed a BBz CAR construct targeting EDB-FN, and the CAR molecule was expressed on the surface of T-cells by lentiviral transduction. In vitro, CAR-T-cells can be activated to express perforin and granzyme and lyse EDB-positive cells (U-87 MG cells, A549 cells, and HUVECs) and have no toxicity to EDB-negative cells (MCF-7). Compared to T-cells, CAR-T-cells can release cytokines after coculture with EDB-positive cell lines. In vivo, CAR-T-cells inhibited the progression of U-87 MG subcutaneous tumors and significantly reduced the blood vessel density in tumor tissue compared to T-cells, without obvious toxicity to mouse tissues and organs. Furthermore, CAR-T-cells overexpressing BiTE targeting EDB-FN can significantly improve their antitumor activity in vitro. (3) Conclusions: These results demonstrate that CAR-T-cells have specific antitumor and angiogenic activities in vivo and in vitro, suggesting that EDB-FN may be a potential solid tumor target for CAR-T therapy. |
format | Online Article Text |
id | pubmed-9496916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94969162022-09-23 CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B Zhang, Zhijie Liu, Chang Yang, Zhe Yin, Hongping Cells Article (1) Background: The lack of specific targets has slowed the progress of CAR-T in treating solid tumors. Recent studies have revealed that EDB-FN (fibronectin extra domain B) may be an effective target for CAR-T treatment of solid tumors; EDB-FN is expressed in tumor and embryonic tissues, and antibody–cytokine fusion proteins targeting EDB-FN have been developed. However, the therapeutic effects of BBz CAR-engineered T-cells targeting EDB-FN in solid tumors have not been evaluated. (2) Results: In this study, we constructed a BBz CAR construct targeting EDB-FN, and the CAR molecule was expressed on the surface of T-cells by lentiviral transduction. In vitro, CAR-T-cells can be activated to express perforin and granzyme and lyse EDB-positive cells (U-87 MG cells, A549 cells, and HUVECs) and have no toxicity to EDB-negative cells (MCF-7). Compared to T-cells, CAR-T-cells can release cytokines after coculture with EDB-positive cell lines. In vivo, CAR-T-cells inhibited the progression of U-87 MG subcutaneous tumors and significantly reduced the blood vessel density in tumor tissue compared to T-cells, without obvious toxicity to mouse tissues and organs. Furthermore, CAR-T-cells overexpressing BiTE targeting EDB-FN can significantly improve their antitumor activity in vitro. (3) Conclusions: These results demonstrate that CAR-T-cells have specific antitumor and angiogenic activities in vivo and in vitro, suggesting that EDB-FN may be a potential solid tumor target for CAR-T therapy. MDPI 2022-09-14 /pmc/articles/PMC9496916/ /pubmed/36139437 http://dx.doi.org/10.3390/cells11182863 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Zhijie Liu, Chang Yang, Zhe Yin, Hongping CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B |
title | CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B |
title_full | CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B |
title_fullStr | CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B |
title_full_unstemmed | CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B |
title_short | CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B |
title_sort | car-t-cell therapy for solid tumors positive for fibronectin extra domain b |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496916/ https://www.ncbi.nlm.nih.gov/pubmed/36139437 http://dx.doi.org/10.3390/cells11182863 |
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