Abstract 6979: An immune-competent, durable MB49-Luc orthotopic bladder cancer model demonstrates bladder-specific tumor immunity for translational immunotherapy research

Abstract Background and Objective: Bladder cancer remains a significant health concern in the United States, with approximately 85,000 new cases and 17,000 deaths annually. Nearly 70% of cases present as non-muscle-invasive bladder cancer (NMIBC), commonly treated with transurethral resection followed by intravesical immunotherapy. However, limited and inconsistent responses to current therapies underscore ongoing clinical challenges. To enable effective therapeutic development, a reliable, immune-competent, and longitudinally trackable preclinical model capable of representing the unique immune and physiological features of bladder cancer is essential. Despite decades of effort to refine syngeneic orthotopic bladder cancer models in mice, low tumor take rates and limited in-life study duration remain major challenges. Here, we present a syngeneic orthotopic bladder cancer model with extended in-life monitoring capacity that recapitulates bladder tumor immunity and enables robust immunotherapy evaluation. Method and Result: A luciferase-expressing MB49 cell line was generated via lentiviral transduction. Female C57BL/6 mice were implanted intravesically to establish an orthotopic tumor model. In-life bioluminescence imaging (BLI) using IVIS revealed stable and quantifiable bladder-localized tumor signals for more than 21 days, with a 100% tumor take rate. Tumor presence in the bladder lumen was confirmed by H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6979.