Abstract LB-265: ONO-AE3-208 inhibits myeloid derived suppressor cells and glioma growth

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Myeloid Derived Suppressor Cells (MDSCs) are up-regulated in all known solid tumors and suppress anti-tumor T-cell activity. Our recent studies have demonstrated the ability of monocytic, Ly6C+ MDSCs to promote glioma growth through the activation of cyclooxygenase (COX)-2 pathway, which is responsible for plostaglandin-synthesis. ONO-AE3-208 is an antagonist of the prostaglandin E (EP)-4 receptor, which is an important positive feedback regulator of the COX-2 pathway. We thus examined the ability of ONO-AE3-208 to suppress MDSC activity in gliomas. ONO-AE3-208 treatment in mice bearing established GL261-quad glioma in the brain resulted in complete and persistent rejection of the tumors (n=4). Flow cytometric analysis revealed that gliomas in the ONO-AE3-208-treated mice were infiltrated by fewer numbers of Ly6C+ MDSCs compared with non-treated animals. We subsequently isolated glioma-infiltrating Ly6C+ MDSCs by flow-sorting to address their functions. RT-PCR analysis revealed that the Ly6C+ MDSCs derived from ONO-AE3-208 treated mice expressed lower levels of the Arg1 and Cox2 expression compared to control animals. Consistently, brain infiltrating leukocytes in ONO-AE3-208 treated tumor-bearing mice demonstrated enhanced Ifng expression compared with control mice, suggestive of enhanced T-cell activity. Our data demonstrate that ONO-AE3-208 may be useful in the treatment of glioma patients to suppress Ly6C+ MDSCs and promote anti-tumor immunity. Citation Format: Kohanbash Gary, Erin Straw, Amram Averick, Brian Ahn, Matthew Smith-Cohn, Takayuki Ohkuri, Akemi Kosaka, Hideho Okada. ONO-AE3-208 inhibits myeloid derived suppressor cells and glioma growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-265. doi:10.1158/1538-7445.AM2014-LB-265