Agonist anti-GITR antibody induces CD8 T cell-mediated tumor rejection

3058 Background: Signaling through GITR (glucocorticoid-induced tumor necrosis factor receptor) can abrogate the suppressive effects of CD4+foxp3+ regulatory T cells and co-stimulate activated effector CD4+ and CD8+ T cells. We have previously shown that in vivo GITR ligation using the agonist anti-GITR mAb DTA-1 augments concomitant immunity and immunity generated by active immunization with self- tumor antigens. In the present study, we assessed the activity of anti-GITR mAb used alone, focusing on the effects of GITR ligation on CD8+ T cells during tumor growth. Methods: C57BL/6 mice were injected intradermally with B16 melanoma and received 1mg of DTA-1 or control rat IgG intraperitoneally on various days after tumor injection. In some experiments, naive, CFSE-labeled pmel-1 CD8+ transgenic T cells (specific for the melanoma antigen gp10025–33 epitope) were transferred into naive recipients 1 day prior to B16 inoculation. Results: DTA-1 treatment on days 0 and 4 led to tumor rejection in 20–30% and 50...