Clin Transl Immunol 2021 Feb 2; 10(2):e1246
Objectives: With a rapidly growing list of candidate immune-based cancer therapeutics, there is a critical need to generate highly reliable animal models to preclinically evaluate the efficacy of emerging immune-based therapies, facilitating successful clinical translation. Our aim was to design and validate a novel
Methods: Tumor xenografts are established rapidly in the greater omentum of globally immunodeficient NOD-
Results: The tumors progress rapidly and disseminate in the mice unless patient-derived tumor-specific T cells are introduced. An initial T cell-mediated tumor arrest is later followed by a tumor escape, which correlates with the upregulation of the checkpoint molecules programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG3) on T cells. Treatment with immune-based therapies that target these checkpoints, such as anti-PD-1 antibody (nivolumab) or interleukin-12 (IL-12), prevented or delayed the tumor escape. Furthermore, IL-12 treatment suppressed PD-1 and LAG3 upregulation on T cells.
Conclusion: Together, these results validate the X-mouse model and establish its potential to preclinically evaluate the therapeutic efficacy of immune-based therapies.
Shenoy, Gautam N; Greene, Christopher J; Bhatta, Maulasri; Baroja, Miren L; Loyall, Jenni L; Balu-Iyer, Sathy V; Kelleher, Raymond J; Carreno, Beatriz M; Linette, Gerald P; Shultz, Leonard D.; and Bankert, Richard B, "Preclinical evaluation of cancer immune therapy using patient-derived tumor antigen-specific T cells in a novel xenograft platform." (2021). Faculty Research 2021. 55.