title: A fully human monoclonal antibody targeting PD-L1 with potent anti-tumor activity.
abstract: 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 0.2 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 177.9h in cynomolgus monkeys.
  
  
  CONCLUSIONS
  mAb B60-55 is a potential candidate for clinical development in cancer treatment.
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China; Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luan
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Dafei
authors.initials: D
authors.lastname: Chai
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Peng
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Ma
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Fu
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Pan
authors.affiliation: Alphamab Co. Ltd., Suzhou, Jiangsu 215125, PR China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China. Electronic address: qin92244@163.com.
authors.forename: Songbing
authors.initials: S
authors.lastname: Qin
authors.affiliation: DingFu Biotarget Co. Ltd., Suzhou, Jiangsu 215125, PR China; Alphamab Co. Ltd., Suzhou, Jiangsu 215125, PR China. Electronic address: tingxu@dingfubio.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology* / Q000302:isolation & purification; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000970:Antineoplastic Agents / Q000276:immunology* / Q000302:isolation & purification; D060890:B7-H1 Antigen / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008252:Macaca fascicularis; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D011485:Protein Binding / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: B60-55; Monoclonal antibody; PD-L1; Therapeutic agent; Tumor