Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitro
Abstract Although immune checkpoint inhibitors have changed the treatment paradigm for non-small cell lung cancer (NSCLC), not all patients benefit from them. Therefore, there is an urgent need to explore novel immune checkpoint inhibitors. Neuropilin-1 (Nrp-1) is a unique immune checkpoint capable...
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Springer
2025-01-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03893-1 |
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| author | Bo Zhang Qin Liu Lin Li Yingchun Ye Xiyuan Guo Wenfeng Xu Ligang Chen Xianming Mo Siji Nian Qing Yuan |
| author_facet | Bo Zhang Qin Liu Lin Li Yingchun Ye Xiyuan Guo Wenfeng Xu Ligang Chen Xianming Mo Siji Nian Qing Yuan |
| author_sort | Bo Zhang |
| collection | DOAJ |
| description | Abstract Although immune checkpoint inhibitors have changed the treatment paradigm for non-small cell lung cancer (NSCLC), not all patients benefit from them. Therefore, there is an urgent need to explore novel immune checkpoint inhibitors. Neuropilin-1 (Nrp-1) is a unique immune checkpoint capable of exerting antitumor effects through CD8+ T cells. It is also a T-cell memory checkpoint that regulates long-term antitumor immunity. However, its role in NSCLC remains unclear. The aim of this study was to develop a fully human anti-Nrp-1 antibody with therapeutic effects against NSCLC in vitro and in vivo. We screened and constructed of a high-affinity anti-Nrp-1 IgG antibody from a constructed high-capacity fully human single-chain fragment variable (scFv) phage library. This novel anti-Nrp-1 IgG antibody partially restored the killing function of exhausted CD8+ T cells in malignant pleural fluid in vitro. Co-culture of peripheral blood mononuclear cells (PBMC) with A549 and the addition of anti-Nrp1-IgG enhanced the killing of A549 target cells, leading to an increase in late-stage apoptosis of target cells. Importantly, anti-Nrp1-IgG treatment significantly reduced tumor volume in a mouse model of lung cancer with humanized immune system. These findings suggest that 53-IgG has a promising application as a potent Nrp-1-targeting agent in NSCLC immunotherapy. |
| format | Article |
| id | doaj-art-95a0c870566b4cdba0e02c33d6320222 |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-95a0c870566b4cdba0e02c33d63202222025-08-20T03:10:17ZengSpringerCancer Immunology, Immunotherapy1432-08512025-01-0174211810.1007/s00262-024-03893-1Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitroBo Zhang0Qin Liu1Lin Li2Yingchun Ye3Xiyuan Guo4Wenfeng Xu5Ligang Chen6Xianming Mo7Siji Nian8Qing Yuan9Public Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical UniversityPublic Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical UniversityPublic Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical UniversityPublic Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical UniversityPublic Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical UniversityPublic Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for NeurosurgeryDepartment of Gastrointestinal Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityPublic Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical UniversityPublic Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical UniversityAbstract Although immune checkpoint inhibitors have changed the treatment paradigm for non-small cell lung cancer (NSCLC), not all patients benefit from them. Therefore, there is an urgent need to explore novel immune checkpoint inhibitors. Neuropilin-1 (Nrp-1) is a unique immune checkpoint capable of exerting antitumor effects through CD8+ T cells. It is also a T-cell memory checkpoint that regulates long-term antitumor immunity. However, its role in NSCLC remains unclear. The aim of this study was to develop a fully human anti-Nrp-1 antibody with therapeutic effects against NSCLC in vitro and in vivo. We screened and constructed of a high-affinity anti-Nrp-1 IgG antibody from a constructed high-capacity fully human single-chain fragment variable (scFv) phage library. This novel anti-Nrp-1 IgG antibody partially restored the killing function of exhausted CD8+ T cells in malignant pleural fluid in vitro. Co-culture of peripheral blood mononuclear cells (PBMC) with A549 and the addition of anti-Nrp1-IgG enhanced the killing of A549 target cells, leading to an increase in late-stage apoptosis of target cells. Importantly, anti-Nrp1-IgG treatment significantly reduced tumor volume in a mouse model of lung cancer with humanized immune system. These findings suggest that 53-IgG has a promising application as a potent Nrp-1-targeting agent in NSCLC immunotherapy.https://doi.org/10.1007/s00262-024-03893-1NSCLCNrp-1IgG1 antibodyTumor immunotherapy |
| spellingShingle | Bo Zhang Qin Liu Lin Li Yingchun Ye Xiyuan Guo Wenfeng Xu Ligang Chen Xianming Mo Siji Nian Qing Yuan Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitro Cancer Immunology, Immunotherapy NSCLC Nrp-1 IgG1 antibody Tumor immunotherapy |
| title | Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitro |
| title_full | Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitro |
| title_fullStr | Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitro |
| title_full_unstemmed | Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitro |
| title_short | Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitro |
| title_sort | therapeutic effect of fully human anti nrp 1 antibody on non small cell lung cancer in vivo and in vitro |
| topic | NSCLC Nrp-1 IgG1 antibody Tumor immunotherapy |
| url | https://doi.org/10.1007/s00262-024-03893-1 |
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