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Pharmacological modulation of GITRL/GITR system: therapeutic perspectives.
Giuseppe Nocentini1, Simona Ronchetti, Maria Grazia Petrillo
1Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
British Journal of Pharmacology
|October 28, 2011
Summary
Glucocorticoid-induced TNFR-related protein (GITR) modulation impacts immune responses. Targeting GITR shows promise for treating cancers, infections, and autoimmune diseases, but mouse-human differences require further study.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Glucocorticoid-induced TNFR-related (GITR) is a TNF receptor superfamily member.
- GITR and its ligand (GITRL) regulate T cell activity, influencing immune responses.
- GITR modulation is implicated in cancer, infections, and autoimmune/inflammatory diseases.
Purpose of the Study:
- To review the mechanisms of GITRL/GITR in immune modulation.
- To highlight structural and functional differences between mouse and human GITR systems.
- To discuss pharmacological agents targeting GITR and potential risks.
Main Methods:
- Review of existing literature on GITR function and modulation.
- Analysis of structural and functional studies of mouse and human GITR/GITRL.
- Examination of pharmacological molecules like anti-GITR mAbs and fusion proteins.
Main Results:
- GITR activation by GITRL influences effector and regulatory T cells.
- GITR-Fc ameliorates autoimmune diseases; anti-GITR mAb treats infections and boosts anti-tumor immunity.
- Significant structural and functional differences exist between mouse and human GITR/GITRL systems.
Conclusions:
- GITR modulation offers therapeutic potential for tumors, infections, and autoimmune diseases.
- Anti-GITR monoclonal antibodies (mAbs) and fusion proteins are key pharmacological agents.
- Cross-species differences necessitate further preclinical research for safe and effective clinical translation.
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