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Open Access 01-02-2025 | NSCLC | Research

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

Authors: Bo Zhang, Qin Liu, Lin Li, Yingchun Ye, Xiyuan Guo, Wenfeng Xu, Ligang Chen, Xianming Mo, Siji Nian, Qing Yuan

Published in: Cancer Immunology, Immunotherapy | Issue 2/2025

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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.
Appendix
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Literature
35.
go back to reference Wang L, Sun M, Lin X, Lei Y, Yin Z, Zhou W (2021) Down-regulation of HBXIP inhibits non-small cell lung cancer growth and enhances the anti-tumor immunity of mice by reducing NRP-1. Ann Clin Lab Sci 51:487–493PubMed Wang L, Sun M, Lin X, Lei Y, Yin Z, Zhou W (2021) Down-regulation of HBXIP inhibits non-small cell lung cancer growth and enhances the anti-tumor immunity of mice by reducing NRP-1. Ann Clin Lab Sci 51:487–493PubMed
Metadata
Title
Therapeutic effect of fully human anti-Nrp-1 antibody on non–small cell lung cancer in vivo and in vitro
Authors
Bo Zhang
Qin Liu
Lin Li
Yingchun Ye
Xiyuan Guo
Wenfeng Xu
Ligang Chen
Xianming Mo
Siji Nian
Qing Yuan
Publication date
01-02-2025
Publisher
Springer Berlin Heidelberg
Keywords
NSCLC
NSCLC
Published in
Cancer Immunology, Immunotherapy / Issue 2/2025
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-024-03893-1

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