TNFRSF18/GITR/CD357

TNFRSF18/GITR/CD357 encodes a type I TNF receptor superfamily protein that inhibits TCR-induced apoptosis and functions as an activation-inducible costimulatory receptor for T cells^[1]^[2]. Mechanistically, GITR engages GITRL and uses TRAF-dependent signaling to regulate NF-κB activity, T-cell activation, proliferation, cytokine production, and programmed cell death^[2]^[3]^[4]. In immune regulation, GITR supports thymic regulatory T-cell differentiation and marks activated or functional Treg populations, linking the TNFRSF18/GITR/CD357 pathway to immune tolerance and inflammation models^[5]. Compared with full-length GITR, reported GITR splice variants provide an isoform-level distinction that should be considered when designing assays, antibodies, or expression studies^[6]. Structural studies further show that human and mouse GITR-GITRL complexes share receptor-ligand and receptor-receptor interfaces but form distinct higher-order assemblies, supporting species-aware experimental design^[7]. For experimental applications, agonistic anti-GITR antibody DTA-1 altered regulatory T-cell stability and intratumor accumulation in B16 melanoma models, making GITR agonism useful for studying tumor immune suppression and Treg biology^[8].

References:

[1]. Nocentini G, et al. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6216-21. [Content Brief]

[2]. Kwon B, et al. Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand. J Biol Chem. 1999 Mar 5;274(10):6056-61. [Content Brief]

[3]. Esparza EM, et al. Glucocorticoid-induced TNF receptor, a costimulatory receptor on naive and activated T cells, uses TNF receptor-associated factor 2 in a novel fashion as an inhibitor of NF-kappa B activation. J Immunol. 2005;174(12):7875-7882.

[4]. Ronchetti S, et al. Role of GITR in activation response of T lymphocytes. Blood. 2002 Jul 1;100(1):350-2. [Content Brief]

[5]. Mahmud SA, et al. Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells. Nat Immunol. 2014 May;15(5):473-81. [Content Brief]

[6]. Nocentini G, et al. Identification of three novel mRNA splice variants of GITR. Cell Death Differ. 2000 Apr;7(4):408-10. [Content Brief]

[7]. Wang F, et al. Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions. Nat Commun. 2021 Mar 2;12(1):1378. [Content Brief]

[8]. Cohen AD, et al. Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation. PLoS One. 2010 May 3;5(5):e10436. [Content Brief]

TNFRSF18/GITR/CD357 Related Products (6):

By Type:	Selective (3)
By Effects:	Inhibitors (4) Agonist (1) Activator (1)

Cat. No.	Product Name	Effect	Purity

HY-P99812

Ragifilimab	Agonist	99.32%
Ragifilimab (INCAGN-1876) is an agonist monoclonal antibody targeting the glucocorticoid-induced TNFR-related protein (GITR). Ragifilimab binds to and activates GITR on T cells, which stimulates the immune system to enhance its anti-tumor activity. Ragifilimab can be used for advanced or metastatic solid tumors research.

HY-P991404

AMG-228	Inhibitor
AMG-228 is a human IgG1 monoclonal antibody (mAb) targeting TNFRSF18/GITR/CD357. AMG-228 can be used in advanced solid tumors research.

HY-P991405

EU-102	Inhibitor
EU-102 is a human monoclonal antibody (mAb) targeting TNFSF18. EU-102 can be used in solid tumors research.

HY-P992450

REGN6569	Activator
REGN6569 is a fully human IgG1 monoclonal antibody targeting glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) with high specificity for GITR. REGN6569 exerts stronger in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) against regulatory T cells expressing GITR. REGN6569 selectively depletes regulatory T cells via antibody-dependent cell-mediated cytotoxicity and increases the proportion of proliferative natural killer (NK) cells in peripheral blood. REGN6569 is applicable for advanced solid malignancies. Isotype control: HY-P99001.

HY-P991406

MK-1248	Inhibitor
MK-1248 is a human IgG4 monoclonal antibody (mAb) targeting TNFSF18. MK-1248 enhances the proliferative response of tumor-infiltrating lymphocytes to anti-CD3 stimulation and promotes the production of anti-tumor-associated regulatory cytokines. MK-1248 can be used in solid tumors research.

HY-P992354

FPA154	Inhibitor
FPA154 is a human monoclonal antibody against TNFRSF18/GITR/CD357. FPA154 activates NF-κB via the GITR pathway. FPA154 can be used in solid tumor research. Recommend Isotype Controls: Human IgG1 kappa, Isotype Control (HY-P99001).

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