Abstract 5275: Celecoxib and chloroquine enhance the antitumor effect of immune checkpoint blockade therapy, in a syngeneic mouse model for pancreatic cancer

Abstract

Abstract Immune checkpoint inhibitors (ICIs) have shown impressive clinical activities in some cancer types, but they have yet to demonstrate any meaningful clinical benefit in patients with pancreatic ductal adenocarcinoma (PDAC) except those with microsatellite instability high (MSI-H) tumors. Several recent studies showed that concomitant use of NSAIDs such as celecoxib by patients with certain cancers could improve the survival benefit of ICI treatment (e.g., Sebastian et al, Clin Lung Cancer, 2023;). Furthermore, autophagy inhibitors such as chloroquine were also reported to sensitize pancreatic tumors to the treatment of ICIs in mouse models for PDAC (Yamamoto, et al, Nature, 2020). We recently reported that the combination of chemotherapy (triple combination of nab-paclitaxel + gemcitabine + cisplatin) and a mouse surrogate of the IFc-enhanced anti-CTLA-4 antibody botensilimab, showed significantly improved antitumor activity in immune competent KPC syngeneic mouse model for PDAC [Tanne, et al, Cancer Res (13_Supplement), 2020]. In this study, we sought to determine whether or not the addition of celecoxib and/or chloroquine further improve the antitumor activity of triple chemotherapy and ICI in the syngeneic KPC model. We first found that celecoxib (30mg/kg P.O. QDx21) significantly enhanced the tumor growth inhibition when added to triple chemotherapy (Gemcitabine 70mg/kg I.P., Cisplatin 4mg/kg I.P., Nab-paclitaxel 25mg/kg I.V. days 1,4 and 7) plus the murine equivalents of botensilimab (100ug I.P. BIW for three weeks) and balstilimab (200ug I.P. BIW for three weeks) (p=0.004, N=10). We then performed a pilot study to assess if adding chloroquine could further improve the activity. While adding chloroquine (60mg/kg I.P. QDx21) alone did not significantly affect tumor growth the addition of both chloroquine and celecoxib greatly improve the tumor growth inhibition compared to just the triple chemotherapy and ICIs (p=0.009, N=5). Overall, our data showed that celecoxib or the combination of celecoxib and chloroquine could substantially sensitize the mouse pancreatic tumors to the treatment of chemotherapy and ICIs. (This work was supported in part by the Seena Magowitz Foundation and the Purple Pansies) Citation Format: Jaeger Moore, Dhan Chand, Daniel Levey, Daniel Von Hoff, Haiyong Han. Celecoxib and chloroquine enhance the antitumor effect of immune checkpoint blockade therapy, in a syngeneic mouse model for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5275.