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

Abstract

Abstract While immune checkpoint inhibitors have changed the treatment paradigm for non–small cell lung cancer (NSCLC), not all patients have experienced their benefits. Hence, there is a pressing need to explore novel immune checkpoint inhibitors. Neuropilin-1 (Nrp-1) represents a distinct immune checkpoint capable of exerting antitumor effects through CD8+ T cells. It also serves as a T-cell memory checkpoint that regulates long-term antitumor immunity. However, its role in NSCLC remains unclear. In this study, we aimed to elucidate the increased expression of Nrp-1 on tumor-infiltrating lymphocytes CD8+ T cells within tumor tissues from patients with lung adenocarcinoma. We screened and constructed of high affinity full-length anti-Nrp-1 IgG1 antibody from a constructed high-capaci4ty fully human single chain fragment variable (scFv) phage library. This novel anti-Nrp-1 IgG1 antibody demonstrated the ability to restore depleted CD8+ T cells in malignant pleural fluid in vitro. Furthermore, it exhibited the capacity to kill target cells through peripheral blood mononuclear cells(PBMCs). Importantly, treatment with the anti-Nrp-1 antibody led to a significant reduction in tumor volume in an immune-systemic humanized mouse model of lung cancer. These findings collectively suggest the promising potential of 53-IgG1 as an effective Nrp-1-targeting agent in the immunotherapy of NSCLC.