Patient-derived bladder cancer organoid model to predict sensitivity and feasibility of tailored precision therapy

Abstract

Abstract. Background. Bladder cancer is a common and highly heterogeneous malignant tumor with a relatively poor prognosis. Thus, personalized treatment strategies for bladder cancer are essential for improving patient outcomes. Materials and methods. We developed an efficient 3-dimensional in vitro organoid culture system for bladder cancer organoids (BCOs), which maintains the homology with the original patient tumors and the heterogeneity between different individuals. In addition, we constructed chimeric antigen receptor (CAR)-T cells targeting B7H3 and evaluated the antitumor function of CAR-T cells by coculturing them with BCOs. Results. The BCOs closely resembled the characteristics of human tumors and were used to test individual sensitivity to platinum-based drugs and olaparib therapy. Coculture with CAR-T cells demonstrated specific antigen recognition and immune activation, indicating their potential in immunotherapy. Conclusions. Our study highlights the potential of BCOs to facilitate the development of personalized medicine for bladder cancer and improve the efficiency of drug discovery for bladder cancer therapy.