HX008: a humanized PD-1 blocking antibody with potent antitumor activity and superior pharmacologic properties

MAbs. 2020 Jan-Dec;12(1):1724751. doi: 10.1080/19420862.2020.1724751.


Through reactivating tumor-infiltrating lymphocytes, therapeutics targeting programmed cell death protein 1 (PD-1) demonstrate impressive clinical efficacy in the treatment of multiple cancers. In this report, we characterize HX008, a humanized IgG4S228P anti-PD-1 monoclonal antibody with an engineered Fc domain, in a series of in vitro assays and in vivo studies. In vitro, HX008 binds to human PD-1 with high affinity and potently suppresses the interaction of PD-1 with PD-L1 and PD-L2. The lack of detectable binding to complement C1q and Fc gamma receptor III-a (FcγRIIIa) suggested that HX008 maintained reduced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. A comparable enhancement of cytokine production and NFAT-driven luciferase expression in cell-based assays confirmed that HX008 could promote T-cell function as effectively as Nivolumab. In vivo antitumor activity studies were carried out within two special tumor models: 1) the MiXeno model with an adoptive transfer of human peripheral blood mononuclear cells into HCC827 xenograft mice; and 2) HuGEMM with human PD-1 gene knock-in syngeneic MC38-bearing mice. In both models, HX008 significantly inhibits tumor growth and shows an effective antitumor response comparable to approved anti-PD-1 drugs. Furthermore, in a pharmacokinetics study performed in cynomolgus monkeys, HX008 induced no immune-related adverse events when administered at 10 mg/kg. Although some anti-drug antibody effects were observed in the primate PK study, the safety and favorable pharmacokinetics demonstrated in human clinical trials validate HX008 as a suitable candidate for cancer immunotherapy. Taken together, our studies provide a fairly thorough characterization of HX008 and strong support for its further clinical research and application.

Keywords: Immunotherapy; PD-1; anti-PD-1 antibody; characterization; tumor model.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Immunotherapy / methods
  • Macaca fascicularis
  • Mice
  • Neoplasms / drug therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.