Abstract 585: Colitis in tumor-bearing mice undergoing checkpoint inhibitor therapy

Checkpoint inhibitor (CPI) therapy represents an exciting new treatment option for patients with advanced malignancies. However, several adverse events (AEs) that affect multiple body systems are associated with CPI treatment, including colitis. The mechanisms mediating these AEs remain to be fully elucidated. That mice treated with CPI fail to develop the spectrum of AEs observed in patients hampers the field9s ability to develop supportive care treatment options. Here we sought to examine colitis in tumor bearing mice undergoing CPI therapy. Briefly, naive TH cells and Treg cells were harvested from C57Bl/6 donor mice and were adoptively transferred into RAG2−/- recipients. Animals were inoculated with B16F10 cells into the left flank seven days later. T cell engraftment was assessed after 13 days, and animals were randomized into treatment groups by rate of T cell engraftment; animals were treated Q3D with either vehicle or anti-CTLA4 for an additional four weeks. Animals were monitored for body weight loss and systemic AEs (gastrointestinal, pulmonary, neurological) daily and tumor volume was measured by digital caliper three times per week. Extent of colitis was evaluated by video endoscopy at several timepoints and colitis severity was scored using a 0-4 scale. Animals developed body weight loss approximately two weeks after T cell transfer and CPI treatment increased the severity of body weight loss observed. Colitis was seen by video endoscopy within a similar timeframe. Mean tumor volume was decreased in animals treated with CPI as compared to those treated with vehicle. Diarrhea, pulmonary symptoms, and neurological symptoms were observed in a subset of animals over the study period; anti-CTLA4 treatment increased the overall incidence of pulmonary symptoms. These data demonstrate the utility of this system for assessment of colitis or other AE supportive care treatment options in the context of CPI-treated, tumor-bearing mice. Citation Format: Caitlin S. Parello, Benjamin G. Cuiffo, Kasey Reardon, Alexandria Fusco, Brett Van Dam, Gregory D. Lyng, Stephen T. Sonis. Colitis in tumor-bearing mice undergoing checkpoint inhibitor therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 585.