A fully human monoclonal antibody targeting PD-L1 with potent anti-tumor activity

分类： 生物学 >> 生物物理学 >> 免疫学 提交时间： 2016-05-05

Luan, Yan Chai, Dafei Peng, Jianjian Ma, Shuli Wang, Min Ma, Hui Li, Xiang Fu, Shilong Pan, Xiaolong Xu, Ting Luan, Yan Qin, Songbing Wang, Xiaoxiao Xu, Ting

摘要： Background: Programmed cell death ligand-1 (PD-L1) with its receptor PD-1 pathway is overactivated in many tumors. Inhibiting the interaction of PD-L1 and PD-1 is an attractive strategy to restore tumor-specific T cell immunity for tumor therapy. Methods: A fully human anti-PD-L1 monoclonal antibody (mAb) B60-55 was identified by yeast surface display. The affinity, specificity, activity, and efficacy of mAb B60-55 were investigated in vitro or in vivo. Results: mAb B60-55 (purity >99%) could bind to PD-L1 that is expressed on HEK293 cells with a dissociation constant of 02 nM, and specifically bind to human or cynomolgus macaque PD-L1 without a cross-reaction with murine PD-L1. Moreover, mAb B60-55 is an antagonistic antibody, which can block PD-L1 binding to its receptors, including PD-1 (PDCD1) and B7.1 (CD80). In vitro assays demonstrated the ability of mAb B60-55 to enhance T cell responses and cytokine production in the mixed lymphocyte reaction. In vivo studies showed that administration of mAb B60-55 exhibited a potent antitumor activity toward tumor cell carcinoma xenograft, with a mean half-life of 177.9 h in cynomolgus monkeys. Conclusion: mAb B60-55 is a potential candidate for clinical development in cancer treatment. (C) 2016 Elsevier B.V. All rights reserved.

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