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Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a common malignancy arising from the liver with limited 5-year survival. Thus, there is an urgency to explore new treatment methods. Chimeric antigen receptor T (CAR T) cell therapy is a very promising cancer treatment. Though, several groups have investigate...

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Autores principales: Mao, Li, Su, Sheng, Li, Jia, Yu, Songyang, Gong, Yu, Chen, Changzhou, Hu, Zhiqiang, Huang, Xiaowu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988215/
https://www.ncbi.nlm.nih.gov/pubmed/36883998
http://dx.doi.org/10.1097/CJI.0000000000000460
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author Mao, Li
Su, Sheng
Li, Jia
Yu, Songyang
Gong, Yu
Chen, Changzhou
Hu, Zhiqiang
Huang, Xiaowu
author_facet Mao, Li
Su, Sheng
Li, Jia
Yu, Songyang
Gong, Yu
Chen, Changzhou
Hu, Zhiqiang
Huang, Xiaowu
author_sort Mao, Li
collection PubMed
description Intrahepatic cholangiocarcinoma (ICC) is a common malignancy arising from the liver with limited 5-year survival. Thus, there is an urgency to explore new treatment methods. Chimeric antigen receptor T (CAR T) cell therapy is a very promising cancer treatment. Though, several groups have investigated CAR T cells targeting MUC1 in solid cancer models, Tn-MUC1-targeted CAR T cells have not yet to be reported in ICC. In this study, we confirmed Tn-MUC1 as a potential therapeutic target for ICC and demonstrated that its expression level was positively correlated with the poor prognosis of ICC patients. More importantly, we successfully developed effective CAR T cells to target Tn-MUC1-positive ICC tumors and explored their antitumor activities. Our results suggest the CAR T cells could specifically eliminate Tn-MUC1-positive ICC cells, but not Tn-MUC1-negative ICC cells, in vitro and in vivo. Therefore, our study is expected to provide new therapeutic strategies and ideas for the treatment of ICC.
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spelling pubmed-99882152023-03-07 Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma Mao, Li Su, Sheng Li, Jia Yu, Songyang Gong, Yu Chen, Changzhou Hu, Zhiqiang Huang, Xiaowu J Immunother Basic Studies Intrahepatic cholangiocarcinoma (ICC) is a common malignancy arising from the liver with limited 5-year survival. Thus, there is an urgency to explore new treatment methods. Chimeric antigen receptor T (CAR T) cell therapy is a very promising cancer treatment. Though, several groups have investigated CAR T cells targeting MUC1 in solid cancer models, Tn-MUC1-targeted CAR T cells have not yet to be reported in ICC. In this study, we confirmed Tn-MUC1 as a potential therapeutic target for ICC and demonstrated that its expression level was positively correlated with the poor prognosis of ICC patients. More importantly, we successfully developed effective CAR T cells to target Tn-MUC1-positive ICC tumors and explored their antitumor activities. Our results suggest the CAR T cells could specifically eliminate Tn-MUC1-positive ICC cells, but not Tn-MUC1-negative ICC cells, in vitro and in vivo. Therefore, our study is expected to provide new therapeutic strategies and ideas for the treatment of ICC. Lippincott Williams & Wilkins 2023-04 2023-03-08 /pmc/articles/PMC9988215/ /pubmed/36883998 http://dx.doi.org/10.1097/CJI.0000000000000460 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Basic Studies
Mao, Li
Su, Sheng
Li, Jia
Yu, Songyang
Gong, Yu
Chen, Changzhou
Hu, Zhiqiang
Huang, Xiaowu
Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma
title Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma
title_full Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma
title_fullStr Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma
title_full_unstemmed Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma
title_short Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma
title_sort development of engineered car t cells targeting tumor-associated glycoforms of muc1 for the treatment of intrahepatic cholangiocarcinoma
topic Basic Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988215/
https://www.ncbi.nlm.nih.gov/pubmed/36883998
http://dx.doi.org/10.1097/CJI.0000000000000460
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