Abstract 54: Comparative preclinical antitumor assessment of 5FU versus anti-PD1 using in vivo imaging system in MC38 orthotopic tumor model

Abstract Immunotherapy has evolved as potential and practical therapeutic options for primary and metastatic tumors. Orthotopically implanted tumor models are clinically relevant and however growth monitoring of orthotopic tumor & assessing efficacy outcomes poses a practical challenge. Optical imaging by In Vivo Imaging System (IVIS) is a valuable method to monitor the real time progression of in vivo tumor growth without implying the need for interim termination during the study. In the present study, we have evaluated the preclinical efficacy of 5- Fluorouracil in combination with mouse anti-PD1 antibody in orthotopic MC38 model in immunocompetent mice. Subcutaneous tumor was generated in donor mice by inoculation of MC38 luciferase reporter cell line. Tumor fragments (∼30mg) harvested from the donor mice were orthotopically implanted on the subserosal layer of cecum of C57BL/6 mice. Tumor growth was monitored twice weekly by IVIS optical imaging system. Mice were randomized based on total flux signal intensity (1-3 X 106 photons/second). Standalone & combination treatment was initiated with 5-FU; 25 mg/kg, i.p; Q2D and anti-PD-1 at 5 mg/kg, ip; Q4D x 4 doses. Total flux (photons/second), changes in body weight, clinicals signs, mortality were monitored twice weekly up to 2 weeks. At the end of the study, ex vivo bioluminescence signal intensity and tumor weights were recorded. In the current MC38 orthotopic tumor model, standalone treatment of anti-PD-1 and 5-FU resulted in moderate tumor regression. However, combination of 5-FU with anti-PD1 resulted in improved efficacy when compared with individual treatments which was evident from the reduction in signal intensity. In conclusion, evaluating efficacy of combinations treatment in preclinical orthotopic tumor models using IVIS imaging will be helpful tool for an accurate, non-invasive longitudinal monitoring of tumor growth over extended duration. Citation Format: Balaji Ramachandran, Ravindra Ghodke, Satheeshkumar Rajendiran, Bhanupranav Skanda, Krishnappa Haladasappa, Sachin Joshi. Comparative preclinical antitumor assessment of 5FU versus anti-PD1 using in vivo imaging system in MC38 orthotopic tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 54.