Journal
INVESTIGATIONAL NEW DRUGS
Volume 37, Issue 5, Pages 799-809Publisher
SPRINGER
DOI: 10.1007/s10637-018-0678-6
Keywords
Oral squamous cell carcinomas; Monoclonal antibody; PD-1; PD-L1
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Funding
- National Natural Science Foundation of China [81001205, 81472179, 81873975]
- Three-year Planning for Strengthening the Construction of Public Health System in Shanghai (2015-2017) [15GWZK0301]
- Fundamental Research Funds for the Central Universities [22120170071]
- Excellent Academic Leader Training Program of Shanghai Health System [2018BR31]
- Clinical Research and Cultivation Project of Shanghai Tongji Hospital [ITJ (ZD) 1803]
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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-H1 and C-L 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.
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