Abstract 3216: Anti-PD-1, Anti-PD-L1 and Anti-CTLA-4 checkpoint inhibitor treatment leads to different responses in syngeneic tumor models

Abstract

Abstract Checkpoint inhibitor treatment has already become a common therapy of various cancer types. Still there is a growing need for well-characterized preclinical mouse models, as clinical data indicate that patients only partially respond to this regiment. We examined the efficacy of anti-CTLA-4, anti-PD-1 and anti-PD-L1 therapy on 4T1, B16.F10, Clone M-3, CT26wt, LL/2, MC38-CEA and RENCA syngeneic tumor models. The outcome demonstrates a large variation in the response to the immune checkpoint therapy among the analyzed tumor models. Poorly immunogenic models like the LL/2 tumor did not respond to any given therapy, whereas highly immunogenic tumor models like CT26wt or MC38-CEA tumors were inhibited by all tested immunotherapies. The CT26wt tumor model was further characterized in a re-challenge experiment. Growth retardation was observed in CT26wt-tumor bearing mice treated with anti-PD-L1 antibody. A fraction of mice responded with a complete regression of the tumor. These mice were repeatedly challenged subcutaneously with a high number of fresh CT26wt tumor cells. No re-growth of CT26 tumors was observed, whereas challenging with fresh 4T1 tumor cells resulted in a rapid 4T1 growth in these mice, demonstrating a specific immune protection against CT26wt tumors. In addition all syngeneic tumor models were analyzed for the distribution of immune cells such as Treg cells, M1/M2 macrophages and M/PMN-MDSCs in tumor tissue based on multi-color flow-cytometric analysis. These data may help to select a suitable model for testing new drug candidates and define a sensitive combination therapy to support the anti-tumor immune defense in addition to checkpoint inhibitor treatment. Citation Format: Peter Jantscheff, Cynthia Schaefer-Obodozie, Sandra Moor, Holger Weber. Anti-PD-1, Anti-PD-L1 and Anti-CTLA-4 checkpoint inhibitor treatment leads to different responses in syngeneic tumor models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3216.