Developing a panel of orthotopic syngeneic tumor models for IO drug discovery

The efficacy of immuno-oncology therapies needs to be evaluated in animal models with functional immune systems. Syngeneic tumor models are established by inoculating mouse cancer cell lines into immunocompetent mice with the same genetic background. The host mice have complete immune activity and show histocompatibility with homograft tumor tissues, which can maximize the simulation of the real tumor microenvironment. Subcutaneous syngeneic models are easily established and have been widely used; however, the subcutaneous tumors lack organ-specific stromal-tumor interactions that are critical for disease progression in patients.

Orthotopic tumor models are established in organ-specific sites, facilitating metastatic spread, supporting immune and stromal component interactions, and providing a more disease-relevant tumor microenvironment for IO therapy assessment. In order to facilitate the development of new immuno-oncology therapies, we have established a panel of orthotopic syngeneic tumor models. We generated a series of luciferase-labeled bioluminescent mouse tumor cell lines, which were then engrafted into the organ of interest to establish orthotopic models. Bioluminescent imaging (BLI) enabled non-invasive in vivo imaging of orthotopic tumor burden, the real time tumor growth, and the response to therapies, monitored by quantitative bioluminescent signals.

Overall, these established orthotopic syngeneic tumor models recapitulate the clinically relevant tumor microenvironment and serve as a useful tool in the preclinical evaluation of immunotherapies.

5 Orthotopic syngeneic models_6024_Gaoxiang

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