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Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma

Cisplatin is a first-line chemotherapy drug for lung adenocarcinoma (LUAD). However, its therapeutic efficacy is limited because of serious side effects and acquired drug resistance. Targeting HER2 has been proven to be a viable therapeutic strategy against LUAD. Moreover, inetetamab, an innovative...

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Autores principales: Cui, Jinfang, He, Yuchao, Zhu, Fuyi, Gong, Wenchen, Zuo, Ran, Wang, Yu, Luo, Yi, Chen, Liwei, Wang, Chengmeng, Huo, Gengwei, Lu, Hailing, Liu, Zhiyong, Chen, Peng, Guo, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496496/
https://www.ncbi.nlm.nih.gov/pubmed/37705753
http://dx.doi.org/10.7150/ijbs.82980
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author Cui, Jinfang
He, Yuchao
Zhu, Fuyi
Gong, Wenchen
Zuo, Ran
Wang, Yu
Luo, Yi
Chen, Liwei
Wang, Chengmeng
Huo, Gengwei
Lu, Hailing
Liu, Zhiyong
Chen, Peng
Guo, Hua
author_facet Cui, Jinfang
He, Yuchao
Zhu, Fuyi
Gong, Wenchen
Zuo, Ran
Wang, Yu
Luo, Yi
Chen, Liwei
Wang, Chengmeng
Huo, Gengwei
Lu, Hailing
Liu, Zhiyong
Chen, Peng
Guo, Hua
author_sort Cui, Jinfang
collection PubMed
description Cisplatin is a first-line chemotherapy drug for lung adenocarcinoma (LUAD). However, its therapeutic efficacy is limited because of serious side effects and acquired drug resistance. Targeting HER2 has been proven to be a viable therapeutic strategy against LUAD. Moreover, inetetamab, an innovative anti-HER2 monoclonal antibody, has a more potent antibody-dependent cell-mediated cytotoxicity (ADCC)-inducing effect than trastuzumab, which has been shown to be an effective and rational strategy in the clinic when combined with multiple chemotherapeutic agents. Thus, the present study aimed to explore the synergistic effects of cisplatin (DDP) and inetetamab in LUAD cells and investigate the detailed underlying mechanisms. Here, in vitro and in vivo, we found that the combination of inetetamab and cisplatin induced synergistic effects, including induction of pyroptosis, in LUAD. Mechanistic studies revealed that inetetamab combined with cisplatin inhibited HER2/AKT/Nrf2 signaling to increase ROS levels, which triggered NLRP3/caspase-1/GSDMB-mediated pyroptosis to synergistically enhance antitumor efficacy in LUAD cells. In addition, cisplatin enhanced the PBMC-killing ability of inetetamab by inducing GSDMB-mediated pyroptosis, which can be explained by increased secretion of IFN-γ. Our study reveals that the anti-HER2 monoclonal antibody inetetamab may be an attractive candidate for LUAD therapy, which opens new avenues for therapeutic interventions for LUAD.
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spelling pubmed-104964962023-09-13 Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma Cui, Jinfang He, Yuchao Zhu, Fuyi Gong, Wenchen Zuo, Ran Wang, Yu Luo, Yi Chen, Liwei Wang, Chengmeng Huo, Gengwei Lu, Hailing Liu, Zhiyong Chen, Peng Guo, Hua Int J Biol Sci Research Paper Cisplatin is a first-line chemotherapy drug for lung adenocarcinoma (LUAD). However, its therapeutic efficacy is limited because of serious side effects and acquired drug resistance. Targeting HER2 has been proven to be a viable therapeutic strategy against LUAD. Moreover, inetetamab, an innovative anti-HER2 monoclonal antibody, has a more potent antibody-dependent cell-mediated cytotoxicity (ADCC)-inducing effect than trastuzumab, which has been shown to be an effective and rational strategy in the clinic when combined with multiple chemotherapeutic agents. Thus, the present study aimed to explore the synergistic effects of cisplatin (DDP) and inetetamab in LUAD cells and investigate the detailed underlying mechanisms. Here, in vitro and in vivo, we found that the combination of inetetamab and cisplatin induced synergistic effects, including induction of pyroptosis, in LUAD. Mechanistic studies revealed that inetetamab combined with cisplatin inhibited HER2/AKT/Nrf2 signaling to increase ROS levels, which triggered NLRP3/caspase-1/GSDMB-mediated pyroptosis to synergistically enhance antitumor efficacy in LUAD cells. In addition, cisplatin enhanced the PBMC-killing ability of inetetamab by inducing GSDMB-mediated pyroptosis, which can be explained by increased secretion of IFN-γ. Our study reveals that the anti-HER2 monoclonal antibody inetetamab may be an attractive candidate for LUAD therapy, which opens new avenues for therapeutic interventions for LUAD. Ivyspring International Publisher 2023-08-06 /pmc/articles/PMC10496496/ /pubmed/37705753 http://dx.doi.org/10.7150/ijbs.82980 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Cui, Jinfang
He, Yuchao
Zhu, Fuyi
Gong, Wenchen
Zuo, Ran
Wang, Yu
Luo, Yi
Chen, Liwei
Wang, Chengmeng
Huo, Gengwei
Lu, Hailing
Liu, Zhiyong
Chen, Peng
Guo, Hua
Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma
title Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma
title_full Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma
title_fullStr Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma
title_full_unstemmed Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma
title_short Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma
title_sort inetetamab, a novel anti-her2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496496/
https://www.ncbi.nlm.nih.gov/pubmed/37705753
http://dx.doi.org/10.7150/ijbs.82980
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