Development of preclinical models for therapy development

Frequently used in-vivo tumor mouse models comprise immunocompetent murine (mostly oncogene-driven) models and human xenografts without immune system. Both models do not sufficiently mimic the situation in patients and do not allow representative testing of immunomodulatory approaches. Fraunhofer ITEM in Regensburg is developing optimized patient-derived xenograft (PDX) models which enable us to follow tumor development as well as dissemination of cancer cells in different organs based on patient-derived DTC or CTC. In addition, we concomitantly generate a human immune system in such mice which infiltrates human PDX tumors and develops immune cell phenotypes (e.g. tumor-associated macrophages) as found in patient samples. Our optimized mouse models allow investigation of a much broader spectrum of immune-tumor interactions, as several human immune populations are present. Such double-humanized mouse models present an opportunity to analyze the influence of human immune cells on tumor development, metastasis formation as well as drug therapy responses of human patient-derived tumor cells.