Clinically Relevant Humanized Mouse Models of Metastatic Prostate Cancer Facilitate Therapeutic Evaluation

Abstract

There is tremendous need for improved prostate cancer models. Anatomically and developmentally, the mouse prostate differs from the human prostate and does not form tumors spontaneously. Genetically engineered mouse models lack the heterogeneity of human cancer and rarely establish metastatic growth. Human xenografts are an alternative but must rely on an immunocompromised host. Therefore, we generated prostate cancer murine xenograft models with an intact human immune system (huNOG and huNOG-EXL mice) to test whether humanizing tumor-immune interactions would improve modeling of metastatic prostate cancer and the impact of androgen receptor-targeted and immunotherapies. These mice maintain multiple human immune cell lineages, including functional human T-cells and myeloid cells.