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Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer
BACKGROUND: Non-small cell lung cancer (NSCLC) is a worldwide health threat with high annual morbidity and mortality. Chemotherapeutic drugs such as paclitaxel (PTX) have been widely applied clinically. However, systemic toxicity due to the non-specific circulation of PTX often leads to multi-organ...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262566/ https://www.ncbi.nlm.nih.gov/pubmed/37308954 http://dx.doi.org/10.1186/s12967-023-04206-3 |
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author | Zheng, Wei Zhu, Tianchuan Tang, Lantian Li, Zhijian Jiang, Guanmin Huang, Xi |
author_facet | Zheng, Wei Zhu, Tianchuan Tang, Lantian Li, Zhijian Jiang, Guanmin Huang, Xi |
author_sort | Zheng, Wei |
collection | PubMed |
description | BACKGROUND: Non-small cell lung cancer (NSCLC) is a worldwide health threat with high annual morbidity and mortality. Chemotherapeutic drugs such as paclitaxel (PTX) have been widely applied clinically. However, systemic toxicity due to the non-specific circulation of PTX often leads to multi-organ damage, including to the liver and kidney. Thus, it is necessary to develop a novel strategy to enhance the targeted antitumor effects of PTX. METHODS: Here, we engineered exosomes derived from T cells expressing the chimeric antigen receptor (CAR-Exos), which targeted mesothelin (MSLN)-expressing Lewis lung cancer (MSLN-LLC) through the anti-MSLN single-chain variable fragment (scFv) of CAR-Exos. PTX was encapsulated into CAR-Exos (PTX@CAR-Exos) and administered via inhalation to an orthotopic lung cancer mouse model. RESULTS: Inhaled PTX@CAR-Exos accumulated within the tumor area, reduced tumor size, and prolonged survival with little toxicity. In addition, PTX@CAR-Exos reprogrammed the tumor microenvironment and reversed the immunosuppression, which was attributed to infiltrating CD8(+) T cells and elevated IFN-γ and TNF-α levels. CONCLUSIONS: Our study provides a nanovesicle-based delivery platform to promote the efficacy of chemotherapeutic drugs with fewer side effects. This novel strategy may ameliorate the present obstacles to the clinical treatment of lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04206-3. |
format | Online Article Text |
id | pubmed-10262566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-102625662023-06-15 Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer Zheng, Wei Zhu, Tianchuan Tang, Lantian Li, Zhijian Jiang, Guanmin Huang, Xi J Transl Med Research BACKGROUND: Non-small cell lung cancer (NSCLC) is a worldwide health threat with high annual morbidity and mortality. Chemotherapeutic drugs such as paclitaxel (PTX) have been widely applied clinically. However, systemic toxicity due to the non-specific circulation of PTX often leads to multi-organ damage, including to the liver and kidney. Thus, it is necessary to develop a novel strategy to enhance the targeted antitumor effects of PTX. METHODS: Here, we engineered exosomes derived from T cells expressing the chimeric antigen receptor (CAR-Exos), which targeted mesothelin (MSLN)-expressing Lewis lung cancer (MSLN-LLC) through the anti-MSLN single-chain variable fragment (scFv) of CAR-Exos. PTX was encapsulated into CAR-Exos (PTX@CAR-Exos) and administered via inhalation to an orthotopic lung cancer mouse model. RESULTS: Inhaled PTX@CAR-Exos accumulated within the tumor area, reduced tumor size, and prolonged survival with little toxicity. In addition, PTX@CAR-Exos reprogrammed the tumor microenvironment and reversed the immunosuppression, which was attributed to infiltrating CD8(+) T cells and elevated IFN-γ and TNF-α levels. CONCLUSIONS: Our study provides a nanovesicle-based delivery platform to promote the efficacy of chemotherapeutic drugs with fewer side effects. This novel strategy may ameliorate the present obstacles to the clinical treatment of lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04206-3. BioMed Central 2023-06-12 /pmc/articles/PMC10262566/ /pubmed/37308954 http://dx.doi.org/10.1186/s12967-023-04206-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zheng, Wei Zhu, Tianchuan Tang, Lantian Li, Zhijian Jiang, Guanmin Huang, Xi Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer |
title | Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer |
title_full | Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer |
title_fullStr | Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer |
title_full_unstemmed | Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer |
title_short | Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer |
title_sort | inhalable car-t cell-derived exosomes as paclitaxel carriers for treating lung cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262566/ https://www.ncbi.nlm.nih.gov/pubmed/37308954 http://dx.doi.org/10.1186/s12967-023-04206-3 |
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