TNFRSF18 (TNF Receptor Superfamily Member 18) is also known as Glucocorticoid-induced TNFR-related protein (GITR), which is expressed on many immune cells including T cells. As a co-stimulatory signal of T cells, TNFRSF18 is upregulated upon the activation of T cells, and in turn promotes T cell proliferation. CD25+/CD4+ regulatory T cell is known to mediate immune tolerance, and GITR agonist antibodies can reverse this immune tolerance, and show anti-tumor effect in multiple tumor models.
Protein Expression Analysis
Splenocytes from both wild type (WT) C57BL/6 and heterozygous B-hGITR mice were analyzed. Mouse GITR+ T cells were detectablby flow cytometrye in both WT C57BL/6 and heterozygous B-hGITR mice, while human GITR+ T cells were only detectable in the heterozygous B-hGITR mice.
Human GITR mAb efficacy evaluation (MC38 cell line)
Murine colon cancer MC38 cells were subcutaneously implanted into heterozygous B-hGITR mice. Mice were grouped when the tumor size was approximately 150±50 mm3 (n=6). Three human GITR antibodies differentlially inhibited tumor growth, confirming that the B-hGITR mouse model is a powerful tool for in vivo GITR antibody pharmacological efficacy studies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.
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