Abstract LB162: 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. Implications: To the best of our knowledge, results illustrate the first model of human prostate cancer that has an intact human immune system, metastasizes to clinically relevant locations, responds appropriately to standard-of-care hormonal therapies, and can model both an immunosuppressive and checkpoint-inhibition responsive immune microenvironment. Citation Format: Raymond J. Kostlan, John T. Phoenix, Audris Budreika, Marina G. Ferrari, Neetika Khurana, Jae Eun Choi, Kristin Juckette, Somnath Mahapatra, Brooke L. McCollum, Russell Moskal, Rahul Mannan, Yuanyuan Qiao, Donald J. Vander Griend, Arul M. Chinnaiyan, Steven Kregel. Clinically relevant humanized mouse models of metastatic prostate cancer facilitate therapeutic evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB162.