Abstract 5176: Orthotopic syngeneic tumor models for preclinical evaluation of cancer immunotherapy strategies

Abstract

Abstract Background: The recent successes of cancer immunotherapies have stimulated interest in the potential application of these approaches in many solid and hematologic tumors. Syngeneic tumor models have been widely used in cancer immunotherapy assessment. However, most of these experimental models were established as subcutaneous models, while there may be significant difference in immune microenvironment comparing orthotopic vs. subcutaneous tumors. In addition, drug delivery and metabolism are different in orthotopic tumors vs. subcutaneous tumors. To address this unmet need, we set out to validate a panel of orthotopic syngeneic models for anti-cancer therapeutics (mainly immunotherapeutics) evaluation. Results: A large collection of orthotopic syngeneic models covering breast cancer, liver cancer and various hematological cancers were established in immunocompetent mice. Survival curves were established and the responsiveness to anti-PD1, anti-PDL1 and anti-CTLA4 antibodies were evaluated in the orthotopic models. Orthotopic liver tumors were monitored with ultrasound imaging to obtain longitudinal growth curves. The correlation in drug efficacy between the orthotopic model and its subcutaneous counterpart was analyzed. The role of NK cells in the development of a panel of systemic hematological tumor models was investigated with NK depleting antibodies. Conclusion: Despite the obvious difficulties, orthotopic syngeneic models represent closer model systems to human diseases and may be a valuable tool to the evaluation of cancer immunotherapies and their combination strategies. Citation Format: Juan Zhang, Sheng Guo, Zhensheng Wang, zhongliang Li, Meng Qiao, Qian Shi. Orthotopic syngeneic tumor models for preclinical evaluation of cancer immunotherapy strategies. [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 5176.