Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Zhijie, Liu, Chang, Yang, Zhe, Yin, Hongping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784794388523646976
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
work_keys_str_mv AT zhangzhijie cartcelltherapyforsolidtumorspositiveforfibronectinextradomainb
AT liuchang cartcelltherapyforsolidtumorspositiveforfibronectinextradomainb
AT yangzhe cartcelltherapyforsolidtumorspositiveforfibronectinextradomainb
AT yinhongping cartcelltherapyforsolidtumorspositiveforfibronectinextradomainb