Abstract 3362: Systematic evaluation of immune checkpoint inhibitors

Abstract

Abstract With the increasing success and subsequent interest in tumor immunology, we recognized a growing need for well-characterized preclinical models. While the literature contains many different experimental models, the available data includes a variety of reagents and the side by side comparative evaluation of therapeutics in multiple models is relatively rare. Lechner et al., (J. Immunother. 36:477-489, 2013) addressed this issue and reported on a comparative analysis of a set of six syngeneic models. Our effort looked to expand this paradigm towards a comparative evaluation of the responsiveness of a collection of syngeneic models to antibody based checkpoint inhibitor therapeutics. Specifically, we examined the response of the Colon26, MC38, B16F10, Lewis Lung, Madison109, EMT-6, and 4T1 models to anti-CTLA-4, anti-PD-1 and anti-PDL-1 monotherapies as well as capturing the response to combination therapies of anti-CTLA-4 with anti-PD-1 or anti-PDL-1.. Our results clearly show a differential response across this set of models both in regard to CTLA-4 targeted therapy as well as PD-1/PDL-1 therapy. In an attempt to expand the number of checkpoint inhibitor responsive models, we are performing a second phase of work evaluating the impact of immuno-modulatory radiation therapy upon these baseline responses. In initiating these studies and evaluating the literature, it became clear that there were multiple choices in regard to anti-CTLA-4 preclinical reagents. We have also performed a series of studies evaluating the efficacy of multiple anti-CTLA-4 clones as an extension of previously published work which described the variable ability of anti-CTLA-4 clones to deplete tumor Treg populations (Simpson et al. J. Exp. Med. 210(9) 1695-1710, 2013). Our anti-tumor data correlates well with these cell based observations. This differential allows one to match efficacy with model and expands the reagents available for evaluating combination therapies. Citation Format: Sheri Barnes, Paula Miliani de Marval, Jacob Hauser, Tracy Brainard, Daniel Small, Aidan J. Synnott, Robert J. Mullin. Systematic evaluation of immune checkpoint inhibitors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3362. doi:10.1158/1538-7445.AM2015-3362