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Therapeutic effect of fully human anti-Nrp-1 antibody on non-small cell lung cancer in vivo and in vitro

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机构： [1]Public Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, Sichuan Province, China [2]Institute of Nuclear Medicine, Southwest Medical University, Department of Nuclear Medicine, Afliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China [3]Department of Neurosurgery, The Afliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Neurosurgery, Luzhou 646000, Sichuan Province, China [4]Clinical Laboratory, Female and Child Health Care and Family Planning Service Center, Binhai New Area, Tianjin 300450, China [5]Department of Gastrointestinal Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China

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关键词： NSCLC Nrp-1 IgG1 antibody Tumor immunotherapy

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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.© 2024. The Author(s).

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大类 | 2 区医学

小类 | 3 区免疫学 3 区肿瘤学

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第一作者机构： [1]Public Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, Sichuan Province, China [4]Clinical Laboratory, Female and Child Health Care and Family Planning Service Center, Binhai New Area, Tianjin 300450, China

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通讯机构： [1]Public Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, Sichuan Province, China [2]Institute of Nuclear Medicine, Southwest Medical University, Department of Nuclear Medicine, Afliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China

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