Suppr超能文献

一种新型人源化抗 PD-1 单克隆抗体增强口腔鳞状细胞癌的治疗效果。

A novel humanized anti-PD-1 monoclonal antibody potentiates therapy in oral squamous cell carcinoma.

机构信息

Department of Stomatology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200127, China.

Department of Neurosurgery, Shanghai Tongji Hospital, Tongji University, School of Medicine, Shanghai, 200065, China.

出版信息

Invest New Drugs. 2019 Oct;37(5):799-809. doi: 10.1007/s10637-018-0678-6. Epub 2018 Oct 27.

Abstract

Currently, immune checkpoint inhibitors have been shown to extend the survival of many cancer patients. However, few studies have focused on immune checkpoint inhibition for the treatment of patients with oral squamous cell carcinoma (OSCC). Here, by screening at an early stage, we obtained a strain of anti-PD-1 monoclonal antibody (mAb) that targets programmed cell death-1 (PD-1) does not contain the C and C fragment. In this study, the role of our novel mAb was tested in the treatment of OSCC in vitro and in vivo. We found that our novel mAb can significantly augment T cell mediated cytokine secretion, target cellular lytic and apoptotic abilities, and inhibit tumor growth and inflammation in vivo. The PD-L1 blockade was accompanied by the inhibition of AKT and ERK1/2, thus suggesting that the PD-L1/PD-1 signaling pathway may play an important immunopreventive role in the tumorigenic properties of OSCC cells by modulating the AKT and ERK1/2 pathways. Additionally, PD-L1 staining was observed both in human OSCC tissues and normal oral mucous tissue adjacent to the tumor, which occurred at different rates. Taken together, these results indicated that our novel anti-PD-1 mAb may be used as a clinical therapy in human OSCC development and progression.

摘要

目前,免疫检查点抑制剂已被证明能延长许多癌症患者的生存期。然而,很少有研究关注免疫检查点抑制治疗口腔鳞状细胞癌(OSCC)患者。在这里,我们通过早期筛选,获得了一株针对程序性细胞死亡蛋白-1(PD-1)的抗 PD-1 单克隆抗体(mAb),该 mAb 不含有 C 和 C 片段。在本研究中,我们测试了新型 mAb 在体外和体内治疗 OSCC 的作用。我们发现我们的新型 mAb 可以显著增强 T 细胞介导的细胞因子分泌、靶向细胞溶解和凋亡能力,并抑制体内肿瘤生长和炎症。PD-L1 阻断伴随着 AKT 和 ERK1/2 的抑制,因此提示 PD-L1/PD-1 信号通路可能通过调节 AKT 和 ERK1/2 通路在 OSCC 细胞的致瘤特性中发挥重要的免疫预防作用。此外,在人类 OSCC 组织和肿瘤相邻的正常口腔黏膜组织中都观察到了 PD-L1 染色,其发生率不同。总之,这些结果表明,我们的新型抗 PD-1 mAb 可能被用于人类 OSCC 的发展和进展的临床治疗。

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验