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Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer

BACKGROUND: Gastric cancer is one of the most common cancers. Peritoneal carcinomatosis (PC) appears to be the most common pattern of recurrence, and more than half of the GC patients eventually die from PC. Novel strategies for the management of patients with PC are urgently needed. Recently, rapid...

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Autores principales: Dong, Xuhui, Fan, Jiqiang, Xie, Wangxu, Wu, Xiang, Wei, Jia, He, Zhonglei, Wang, Wenxin, Wang, Xueting, Shen, Pingping, Bei, Yuncheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403530/
https://www.ncbi.nlm.nih.gov/pubmed/37386139
http://dx.doi.org/10.1038/s41416-023-02319-6
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author Dong, Xuhui
Fan, Jiqiang
Xie, Wangxu
Wu, Xiang
Wei, Jia
He, Zhonglei
Wang, Wenxin
Wang, Xueting
Shen, Pingping
Bei, Yuncheng
author_facet Dong, Xuhui
Fan, Jiqiang
Xie, Wangxu
Wu, Xiang
Wei, Jia
He, Zhonglei
Wang, Wenxin
Wang, Xueting
Shen, Pingping
Bei, Yuncheng
author_sort Dong, Xuhui
collection PubMed
description BACKGROUND: Gastric cancer is one of the most common cancers. Peritoneal carcinomatosis (PC) appears to be the most common pattern of recurrence, and more than half of the GC patients eventually die from PC. Novel strategies for the management of patients with PC are urgently needed. Recently, rapid progress has been made in adoptive transfer therapy by using macrophages as the effector cells due to their capabilities of phagocytosis, antigen presentation, and high penetration. Here, we generated a novel macrophage-based therapy and investigated anti-tumoral effects on GC and potential toxicity. METHODS: We developed a novel Chimeric Antigen Receptor-Macrophage (CAR-M) based on genetically modifying human peritoneal macrophages (PMs), expressing a HER2-FcεR1γ-CAR (HF-CAR). We tested HF-CAR macrophages in a variety of GC models in vitro and in vivo. RESULTS: HF-CAR-PMs specifically targeted HER2-expressed GC, and harboured the FcεR1γ moieties to trigger engulfment. Intraperitoneal administration of HF-CAR-PMs significantly facilitated the HER2-positive tumour regression in PC mouse model and prolonged the overall survival rate. In addition, the combined use of oxaliplatin and HF-CAR-PMs exhibited significantly augment anti-tumour activity and survival benefit. CONCLUSIONS: HF-CAR-PMs could represent an exciting therapeutic option for patients with HER2-positive GC cancer, which should be tested in carefully designed clinical trials.
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spelling pubmed-104035302023-08-06 Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer Dong, Xuhui Fan, Jiqiang Xie, Wangxu Wu, Xiang Wei, Jia He, Zhonglei Wang, Wenxin Wang, Xueting Shen, Pingping Bei, Yuncheng Br J Cancer Article BACKGROUND: Gastric cancer is one of the most common cancers. Peritoneal carcinomatosis (PC) appears to be the most common pattern of recurrence, and more than half of the GC patients eventually die from PC. Novel strategies for the management of patients with PC are urgently needed. Recently, rapid progress has been made in adoptive transfer therapy by using macrophages as the effector cells due to their capabilities of phagocytosis, antigen presentation, and high penetration. Here, we generated a novel macrophage-based therapy and investigated anti-tumoral effects on GC and potential toxicity. METHODS: We developed a novel Chimeric Antigen Receptor-Macrophage (CAR-M) based on genetically modifying human peritoneal macrophages (PMs), expressing a HER2-FcεR1γ-CAR (HF-CAR). We tested HF-CAR macrophages in a variety of GC models in vitro and in vivo. RESULTS: HF-CAR-PMs specifically targeted HER2-expressed GC, and harboured the FcεR1γ moieties to trigger engulfment. Intraperitoneal administration of HF-CAR-PMs significantly facilitated the HER2-positive tumour regression in PC mouse model and prolonged the overall survival rate. In addition, the combined use of oxaliplatin and HF-CAR-PMs exhibited significantly augment anti-tumour activity and survival benefit. CONCLUSIONS: HF-CAR-PMs could represent an exciting therapeutic option for patients with HER2-positive GC cancer, which should be tested in carefully designed clinical trials. Nature Publishing Group UK 2023-06-29 2023-08-24 /pmc/articles/PMC10403530/ /pubmed/37386139 http://dx.doi.org/10.1038/s41416-023-02319-6 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Dong, Xuhui
Fan, Jiqiang
Xie, Wangxu
Wu, Xiang
Wei, Jia
He, Zhonglei
Wang, Wenxin
Wang, Xueting
Shen, Pingping
Bei, Yuncheng
Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer
title Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer
title_full Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer
title_fullStr Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer
title_full_unstemmed Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer
title_short Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer
title_sort efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403530/
https://www.ncbi.nlm.nih.gov/pubmed/37386139
http://dx.doi.org/10.1038/s41416-023-02319-6
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