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Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
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Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups

Lawrence P Andrews1, Hiroshi Yano1,2, Dario A A Vignali3,4

  • 1Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Nature Immunology
|October 16, 2019
PubMed

Insights

Cancer immunotherapies targeting inhibitory receptors (IRs) show promise, but many patients don't respond. Exploring novel IR-ligand pathways, like LAG-3 and TIGIT, could enhance treatment effectiveness.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Current cancer immunotherapies targeting CTLA-4, PD-1, and PD-L1 have limitations, with many patients exhibiting resistance.
  • Novel inhibitory receptors (IRs) such as LAG-3, TIM-3, and TIGIT, and B7 family ligands (B7-H3, B7-H4, B7-H5) are emerging targets.
  • The complex biology and mechanisms of action for these novel targets require further elucidation.

Purpose of the Study:

  • To review the fundamental biology of novel IR-ligand pathways.
  • To assess the current clinical status of immunotherapeutics targeting these novel pathways.
  • To explore combination strategies with existing anti-PD-1/PD-L1 therapies.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of biological mechanisms of novel IR-ligand interactions.
  • Evaluation of clinical trial data for monotherapy and combination treatments.

Main Results:

  • Several novel IRs and ligands are under investigation, with some showing modest clinical success.
  • The optimal design of immunotherapeutics targeting these novel pathways is still under development.
  • Combination therapies involving novel IRs and PD-1/PD-L1 blockade are being explored.

Conclusions:

  • Deeper understanding of the basic biology of novel IR-ligand pathways is crucial.
  • Further research is imperative for developing more effective cancer immunotherapies.
  • Optimizing immunotherapeutic strategies may improve clinical outcomes for non-responsive patients.

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