Abstract C110: Evaluation of immune cell populations in checkpoint inhibitor responsive syngeneic models

Abstract

Abstract Given the increasing success of cancer immunotherapies, we recognized a growing need for well-characterized preclinical models to enable drug discovery efforts. Syngeneic mouse tumor models offer advantages over conventional xenograft models for immunotherapy studies due to the presence of a fully functional immune system. We recently completed a comparative evaluation of the responsiveness of a collection of syngeneic models to two antibody based immunocheckpoint inhibitor therapeutics (anti-CTLA4, anti-PD1). This body of work resulted in the identification of several models responsive to checkpoint inhibition; CT26, Colon26, MC38, EMT-6, and A20. Our results clearly show differential tumor growth responses across this set of models following treatment with CTLA-4 and PD-1 targeted therapy. To further characterize these responses, we have performed a series of studies to identify and track immune cell populations by flow cytometry in blood, spleen, and tumor samples from mice harboring each responsive model. In these studies, we have investigated whether the modulation of CD4+, CD8+, regulatory CD4+ T cells (Treg), and myeloid derived suppressor cells (MDSC) populations correlates with the impact of immunocheckpoint inhibitors on tumor growth over time in untreated and challenged animals. These correlations of flow analyses with our antitumor data can point to the utility of cell-based endpoints as additional tools for evaluating combination outcomes. Citation Format: Sheri Barnes, Marcio Lasaro, Jacob Hauser, Robert J. Mullin, Aidan Synnott. Evaluation of immune cell populations in checkpoint inhibitor responsive syngeneic models. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C110.