Abstract B021: Modeling Human Immune Competent Patient-Derived Metastatic Prostate Cancer in Vivo

Abstract Background: As the most common non-cutaneous form of cancer in males, metastatic prostate cancer is expected to claim the lives of approximately 35,000 Americans in 2025. Notably, the rate of cancer death is highly dependent upon the site of metastasis, and thus the organ site directly affected by this hormone dependent cancer. Despite its prevalence, clinically relevant models recapitulating the histological, phenotypic, and molecular diversity of metastases are scarce and are often done in immune compromised systems. This prevents a detailed evaluation of potential immune effects which is especially relevant in the context of hormone deprivation treatments which may modify immunity. Methods: We have humanized NSG immunocompromised mice that express human Stem Cell Growth Factor, human M-CSF and human IL-3 that have been engrafted with human CD34+ cells (NSG-SGM3). Using both an androgen receptor (AR)-positive adenocarcinoma (PDM136) and a neuroendocrine (NE) prostate cancer (PDMLym1) model, we assessed metastatic properties by inoculating each PDX, via intracardiac injection. Immune engraftment and competence was determined via flow cytometry and response to ovalbumin challenge. Growth of tumors was monitored via bioluminescent imaging of a luciferase transgene expressed in each cell line. Metastatic development was noted in multiple organs. Androgen deprivation was performed before systemic tumor burden exceeded 108 radiance units. Results and Conclusion s: We demonstrate successful adoption of human immune cells in the murine model and the successful growth of tumors at distant metastatic sites. We compared these metastatic tumors to immunocompromised controls, noting differences in human macrophage populations within immunogenic metastatic bone niches before and after removal of testosterone. Given the influence of hormones on immune response in prostate tumors, this immunogenic response varies based on tumor location and hormone exposure. These data provide insight into how we approach combination therapies involving hormone modulation and immune therapies, such as checkpoint inhibition and cytokine traps. Citation Format: John M. Fenimore, Juanjuan Yin, Shana Y. Trostel, Lucas Horn, Ross Lake, Claudia M. Palena, Adam G. Sowalsky. Modeling Human Immune Competent Patient-Derived Metastatic Prostate Cancer in Vivo [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B021.