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Modulation of GITR for cancer immunotherapy

David A Schaer1, Judith T Murphy, Jedd D Wolchok

  • 1Swim Across America Laboratory, Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.

Current Opinion in Immunology
|January 17, 2012
PubMed

Insights

Targeting glucocorticoid-induced tumor necrosis factor receptor (GITR) with agonist antibodies shows promise for cancer immunotherapy. This review covers preclinical research and clinical trials exploring GITR as a novel anti-tumor therapy.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Immune checkpoint modulation is a key strategy in cancer immunotherapy.
  • CTLA-4 blockade has been FDA-approved, validating immune checkpoint inhibition.
  • Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a target within the TNF receptor superfamily.

Purpose of the Study:

  • To review preclinical research on GITR-targeted cancer therapy.
  • To discuss the rationale for clinical trials involving GITR agonists.
  • To highlight GITR as a novel immunotherapeutic target for cancer.

Main Methods:

  • Review of preclinical studies on GITR modulation.
  • Analysis of the scientific rationale for targeting GITR.
  • Overview of ongoing Phase 1 clinical trials for GITR-based cancer immunotherapy.

Main Results:

  • Preclinical data suggest GITR targeting by agonist antibodies or ligand is effective against tumors.
  • GITR modulation activates anti-tumor immune responses.
  • Two Phase 1 clinical trials have been initiated to evaluate GITR-targeted cancer therapy.

Conclusions:

  • Targeting GITR represents a promising new avenue for cancer immunotherapy.
  • Further clinical investigation is warranted to establish GITR's therapeutic potential.
  • GITR agonists offer a novel approach to enhance anti-tumor immunity.

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