816 Predictive modeling of immune-related adverse events using tumoroids

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Background Immunotherapy has revolutionized cancer treatment, yet the emergence of immune-related adverse events (irAEs) poses significant challenges to its widespread adoption. Predicting and managing irAEs is still a critical aspect of patient care. Tumoroids which retain the endogenous tumor microenvironment offer a promising platform to study these events in a controlled setting. Methods In this study, we utilized tumoroids from patient-resected tumors to simulate the dynamic interactions between the tumor cells and immune cells. By subjecting these tumoroids to immune-stimulating agents, including checkpoint inhibitors, we monitored the development of irAEs while characterizing immune cell infiltration, cytokine release patterns, and tumor growth dynamics. Results Our results show a correlation between specific features of the tumoroid models and the occurrence and severity of irAEs observed in clinical settings. Utilizing machine learning algorithms, we developed prognostic models capable of predicting the likelihood and severity of irAEs associated with different immunotherapies and patient profiles. This model offers insights into the underlying mechanisms driving irAEs and helps improve treatment strategies to minimize adverse events while maximizing therapeutic efficacy. Conclusions Nilogen’s ex-vivo 3D tumoroid platforms preserve the unique tumor immune microenvironment and extracellular matrix (ECM), mimicking physiological spatial architecture for comprehensive therapeutic evaluation. These tumoroids are shown to be a valuable tool for predicting immune-related adverse events associated with immunotherapy. This approach offers hope for the future by improving patient outcomes and accelerating the translation of immunotherapeutic interventions into clinical practice. Ethics Approval Ethics approval was obtained through Chesapeak IRB (Pro00014313) which determined ‘Using the Department of Health and Human Services regulations at 45 CFR 46, the IRB determined that this research project does not constitute human subject research and, therefore, does not require IRB oversight.’ Full informed consent was obtained for each tissue used in this study.

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