Abstract 3777: RORγ agonist enhances antitumor effects of immune checkpoint anti-PD1

Abstract

Abstract Anti-PD1/PDL1 therapies have demonstrated great clinical benefit in some cancers, albeit in a limited percentage of patients. RORγt is a master transcription factor, which promotes Type 17 T cell differentiation and is known to enhance the stemness and plasticity of effector cells and to modulate PD1 expression. Since one of the potential failure mechanism of anti-PD1 is the lack of sustained CD8 infiltration within the TME, we assessed whether combining a synthetic, small-molecule RORγ agonist could enhance the antitumor effects of anti-PD1 treatment. To assess this combination treatment, we tested the effects of anti-PD1 antibody (1 mg/kg twice weekly) combined with a RORγ-agonist (LYC-54143; 100 mg/kg PO, BID given continuously till the end of study) in tumor-bearing murine mode lthat utilizes a vaccine for proper priming. We found that RORγ agonist combined with PD1 antibody significantly enhanced the anti-PD1 antitumor effect. This result was manifested by further delaying the tumor growth and prolonging mice survival. At day 35 after tumor implantation, 66% of mice survived in the group treated with anti-PD1 and RORγ agonist and vaccine when compared to 0% survival following anti-PD1 + vaccine or vaccine- alone treatments. This enhanced antitumor activity was observed/confirmed in several tumor models with the combination of RORγ agonist + anti-PD1 treatment. These results show that RORγ agonists may enhance the effectiveness of anti-PD1 therapy and therefore this combination is a promising therapeutic strategy for cancer. Citation Format: Pankaj Gaur, Vivek Verma, Rahul Nandre, Pooja Vir, Hua Wang, Baolin Kang, Laura Carter, Xiao Hu, Xikui Liu, Seema Gupta, Samir Khleif. RORγ agonist enhances antitumor effects of immune checkpoint anti-PD1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3777.