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

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Summary

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 CH1 and CL 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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Funding

This work was supported by the National Natural Science Foundation of China (81001205, 81472179, 81873975), the Three-year Planning for Strengthening the Construction of Public Health System in Shanghai (2015–2017) (15GWZK0301), the Fundamental Research Funds for the Central Universities (22120170071), the Excellent Academic Leader Training Program of Shanghai Health System (2018BR31), and the Clinical Research and Cultivation Project of Shanghai Tongji Hospital [ITJ (ZD) 1803].

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  1. Y. Cai and Fei Wang contributed equally to this work.

Authors and Affiliations

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

    Y. Cai

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

    Fei Wang

  3. Department of Clinical Laboratory, Baoshan Traditional Chinese and Western Medicine Hospital, Shanghai, 201900, China

    Q. Liu

  4. Putuo District Mental Health Center, Shanghai, 200065, China

    Z. Li

  5. Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University, School of Medicine, Shanghai, 200065, China

    D. Li & Z. Sun

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  1. Y. Cai
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All applicable international, national, and/or institutional guidelines for the care and use of animal were followed. All procedures performed in studies involving human participants received ethics approval from the independent Ethics Committee of the Shanghai Ninth People’s Hospital Affliated to Shanghai Jiaotong University School of Medicine (No. 200926). All experimental procedures were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Cai, Y., Wang, F., Liu, Q. et al. A novel humanized anti-PD-1 monoclonal antibody potentiates therapy in oral squamous cell carcinoma. Invest New Drugs 37, 799–809 (2019). https://doi.org/10.1007/s10637-018-0678-6

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