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Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo

HER-2 targeted therapies, such as monoclonal antibodies (mAbs) and CAR-T cell therapy have been applied in the treatment of various of cancers. However, the anti-HER2 CAR-T cell therapy are limited by its expensive production procedure and fatal side effects such as cytokine storm or “On target, off...

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Autores principales: Zhang, Haiqiang, Ye, Xueshuai, Wen, Junye, Cai, Ziqi, Li, Yang, Zhang, Mengya, Shen, Li, Cai, Jianhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213520/
https://www.ncbi.nlm.nih.gov/pubmed/35729189
http://dx.doi.org/10.1038/s41598-022-14336-1
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author Zhang, Haiqiang
Ye, Xueshuai
Wen, Junye
Cai, Ziqi
Li, Yang
Zhang, Mengya
Shen, Li
Cai, Jianhui
author_facet Zhang, Haiqiang
Ye, Xueshuai
Wen, Junye
Cai, Ziqi
Li, Yang
Zhang, Mengya
Shen, Li
Cai, Jianhui
author_sort Zhang, Haiqiang
collection PubMed
description HER-2 targeted therapies, such as monoclonal antibodies (mAbs) and CAR-T cell therapy have been applied in the treatment of various of cancers. However, the anti-HER2 CAR-T cell therapy are limited by its expensive production procedure and fatal side effects such as cytokine storm or “On target, off tumor”. The application of anti-HER2 mAbs to the soild tumor are also plagued by the patients resistant with different mechanisms. Thus, the recombinant protein technology can be presented as an attractive methods in advantage its less toxic and lower cost. In this study, we produced a HER-2-targeting recombinant protein, which is the fusion of the anti-HER-2 single chain fragment variable domain, CCL19 and IL7 (HCI fusion protein). Our results showed that the recombinant protein can induce the specific lysis effects of immune cells on HER-2-positive gastric tumor cells and can suppress gastric tumor growth in a xenograft model by chemotactic autoimmune cell infiltration into tumor tissues and activated T cells. Taken together, our results revealed that the HCI fusion protein can be applied as a subsequent clinical drug in treating HER-2 positive gastric tumors.
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spelling pubmed-92135202022-06-23 Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo Zhang, Haiqiang Ye, Xueshuai Wen, Junye Cai, Ziqi Li, Yang Zhang, Mengya Shen, Li Cai, Jianhui Sci Rep Article HER-2 targeted therapies, such as monoclonal antibodies (mAbs) and CAR-T cell therapy have been applied in the treatment of various of cancers. However, the anti-HER2 CAR-T cell therapy are limited by its expensive production procedure and fatal side effects such as cytokine storm or “On target, off tumor”. The application of anti-HER2 mAbs to the soild tumor are also plagued by the patients resistant with different mechanisms. Thus, the recombinant protein technology can be presented as an attractive methods in advantage its less toxic and lower cost. In this study, we produced a HER-2-targeting recombinant protein, which is the fusion of the anti-HER-2 single chain fragment variable domain, CCL19 and IL7 (HCI fusion protein). Our results showed that the recombinant protein can induce the specific lysis effects of immune cells on HER-2-positive gastric tumor cells and can suppress gastric tumor growth in a xenograft model by chemotactic autoimmune cell infiltration into tumor tissues and activated T cells. Taken together, our results revealed that the HCI fusion protein can be applied as a subsequent clinical drug in treating HER-2 positive gastric tumors. Nature Publishing Group UK 2022-06-21 /pmc/articles/PMC9213520/ /pubmed/35729189 http://dx.doi.org/10.1038/s41598-022-14336-1 Text en © The Author(s) 2022 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/) .
spellingShingle Article
Zhang, Haiqiang
Ye, Xueshuai
Wen, Junye
Cai, Ziqi
Li, Yang
Zhang, Mengya
Shen, Li
Cai, Jianhui
Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo
title Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo
title_full Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo
title_fullStr Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo
title_full_unstemmed Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo
title_short Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo
title_sort anti-her2 scfv-ccl19-il7 recombinant protein inhibited gastric tumor growth in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213520/
https://www.ncbi.nlm.nih.gov/pubmed/35729189
http://dx.doi.org/10.1038/s41598-022-14336-1
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