Realizing the Potential for Recipient Immune Cells in Adoptive Immune Therapy

Despite the extensive use of animal models to better understand disease progress, efficacy and toxicity of therapeutic interventions a vast majority of promising treatments fail in human trials (Holzapfel et al., 2015). One approach has been to humanize mouse model systems to recapitulate disease processes by conditioning mice to permit engraftment of human cells utilizing immune-deficient mice such as NSG strains (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) in pre-clinical studies. One major advantage of this is to allow detailed molecular profiling of diseased cells and targeting aberrant processes for individual patients by growing patient derived cells xenografted into immune-deficient mice (Malaney et al., 2014). However, major shortcoming of humanized xenograft mouse models include: the absence of a tumor microenvironment to study cytokine/chemokine interactions that are critical for cancer progression and metastasis; and toxicity arising from induction of cytokine storms cannot be tested.