Document Type

Article

Publication Date

2-2-2021

Keywords

JMG

JAX Source

Clin Transl Immunol 2021 Feb 2; 10(2):e1246

PMID

33552509

DOI

https://doi.org/10.1002/cti2.1246

Grant

CA034196

Abstract

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.

Comments

This is an open access article under the terms of the Creative Commons Attribution License.

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