GITR, also known as TNFRSF18, CD357 and AITR, is a cell surface receptor constitutively expressed at high levels on Tregs and at low levels on naïve and memory T cells. GITRL (TNFSF18), the ligand of GITR, is also a member of the TNF superfamily and is predominantly expressed by activated antigen-presenting cells (APCs) such as macrophage, dendritic cells (DCs), and activated B cells. The GITR and GITRL pathway is a very important target for immunotherapy drug discovery. The binding of GITR by the GITR ligand activates the immune response by stimulating macrophages and triggering T-cells to expand, proliferate, and differentiate. Using anti-GITR mAb to trigger GITR signaling is effective in treating bacterial, viral, and parasitic infections, as well as in boosting the immune response against tumors. Not surprisingly, clinical trials testing anti-GITR mAb in melanoma patients are already in progress.
Fig.1 Model for GITR modulation of anti-tumor immunity. (Knee, 2016)
Therapeutic Agents in Development and Ongoing Clinical Trials
In syngeneic mouse tumor models, GITR modulation shows compelling antitumor activity, which is attributed to its costimulatory role on CD4+ and CD8+ T cells, as well as inhibition or depletion of intratumoral Tregs. Recently, a number of agents have entered the clinic, including traditional bivalent antibodies and multivalent GITR ligand fusion proteins.
GITR/GITRL pathway is an attractive target for immunotherapy, owing to its capacity to promote effector T cell functions and hamper regulatory T cell suppression. Creative Biolabs has successfully assisted many projects in immune checkpoint research. As a privileged partner, we can help our clients design a roadmap that targets the GITR and GITRL pathway by offering a comprehensive set of highlighted services such as Immune Checkpoint Antibody Development, Immune Checkpoint Targeted Small Molecule Drug Development, Immune Checkpoint Assays . Through this roadmap, we can promote your research project efficiently. Please contact us for detailed information and deeper communication to learn how we can be involved in your projects.
Knee, D. A.; et al. Rationale for anti-GITR cancer immunotherapy. European journal of cancer. 2016, 67: 1-10.
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