Development of Patient-Derived Immuno-Organoids as a Preclinical Platform for Personalized Cancer Immunotherapy to Test Tumor-Specific Immune Responses in Renal Cell Carcinoma and Bladder Cancer 2253

Abstract Description Immunotherapy holds promise for cancer treatment but is often limited by tumor heterogeneity and patient variability. Current preclinical models are either oversimplified or too complex and costly, hindering accurate predictions. To address these issues, we developed Patient-Derived Tumor Organoids (PDTOs), 3D structures from patient tumors that retain original morphology and function, offering a robust ex vivo cancer model. In this study, we used PDTOs from renal cell carcinoma (RCC) and bladder cancer to test precision immunotherapy. Tumor tissues from five patients were characterized for drug sensitivity and cellular markers. We analyzed the immunopeptidomes of patient tumors using ligandome techniques (PeptiCHIP) and bioinformatics. The immunogenicity of MHC I-presented peptides was validated as targets for T cell therapies, and antigen-expanded T cells were assessed for tumor-killing in co-culture experiments. Over 50 peptides relevant to patient tumors were identified, several of which induced antigen-specific CD8+ responses and promoted tumor cell killing. This study presents a promising pipeline for target identification and testing immune responses, advancing precision immunotherapy with a patient-specific preclinical tool. Funding Sources Doctoral schools travel grant - University of Helsinki Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)