Modeling Pancreatic and Non-Small Cell Lung Cancer Using a Humanized Mouse Platform

AACR 2021 -- The development of immuno-oncology agents against human targets is actively pursued in the preclinical space using mice with aspects of the human immune system reconstituted. Mice engrafted with human peripheral blood mononuclear cells (hPBMC) provide a means for investigating human immune-mediated anti-tumor activity. To generate a platform to explore test agents against human targets in the mouse, the human tumor models A549 (non-small cell lung) or MIA PaCa-2 (pancreatic) were characterized in the context of engrafted hPBMCs in the NSG™ mouse. In vitro activation and in vivo persistence of hPBMC donors was determined. Anti-tumor activity of pembrolizumab was investigated in these tumor models. The microenvironment of A549 tumors was analyzed by flow cytometry both for infiltration and distribution of human T cells as well as activation and exhaustion biomarkers.

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