Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer

Curr Opin Investig Drugs. 2010 Dec;11(12):1354-9.


Tumor antigen-specific T-cell function is regulated by both positive and negative costimulatory signals, which are received in the secondary lymphoid organs and within the tumor microenvironment. Tumor-induced T-cell dysfunction results from a lack of positive costimulatory signals, combined with a predominance of negative immunoregulatory mechanisms. The engagement of the protein programmed death 1 (PD1), expressed on activated T-cells, by programmed death ligand 1 (PD-L1)/B7H1 within tumor cells or other host-derived cells results in the downregulation of T-cell function, and represents an important negative regulatory pathway. Preclinical cancer models suggest that interruption of PD1/PD-L1 interactions leads to improved antitumor T-cell responses and tumor control. mAbs developed against both PD1 and PD-L1/B7H1 are being evaluated in phase I/II clinical trials in patients with a variety of cancers. The uncoupling of negative immune regulatory pathways therefore represents an exciting and potentially highly valuable new modality for cancer immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / immunology
  • Apoptosis Regulatory Proteins / metabolism
  • B7-H1 Antigen
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Female
  • Humans
  • Immunotherapy
  • Male
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Nivolumab
  • Programmed Cell Death 1 Receptor
  • Signal Transduction
  • T-Lymphocytes / immunology
  • Tumor Microenvironment


  • Antibodies, Monoclonal
  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab