ArticleJournal of translational medicine2026
Real-time monitoring of CAR T cell dynamics in tumor patient-derived organoids using the OrganoIDNet algorithm.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPatient-derived organoids (PDOs) provide physiologically relevant 3D tumor models for preclinical drug testing, yet robust and automated methods to quantify dynamic responses to immunotherapies remain limited. OrganoIDNet is a deep learning-based image analysis framework that enables automated, label-free segmentation and longitudinal quantification of organoid morphology. Here, we extend the application of OrganoIDNet to evaluate chimeric antigen receptor (CAR) T cell activity against pancreatic ductal adenocarcinoma (PDAC) PDOs targeting the tumor-associated antigen CD318.
resultsCD318-directed CAR T cells were co-cultured with PDAC PDOs using a Matrigel-based sandwich system and monitored by time-lapse bright-field imaging. OrganoIDNet enabled accurate single-organoid segmentation and continuous quantification of organoid number and area across multiple effector-to-target ratios. CAR-318 T cells induced robust, antigen-dependent cytotoxicity, characterized by progressive reductions in organoid number and size and were accompanied by increased T cell activation marker expression and changes in TIM-3 expression at the endpoint. Dynamic imaging and T cell spatial analysis, further revealed close T cell-organoid interactions and early tumor cell elimination, providing time-resolved information on organoid responses and T cell proximity that complements conventional endpoint assays.
conclusionsBy integrating organoid-immune co-cultures with OrganoIDNet-driven live-cell imaging, we established an automated longitudinal imaging assay for assessing CAR T cell-mediated responses in PDAC PDOs. The assay enabled continuous quantification of organoid number and area, together with image-based assessment of T cell proximity, across multiple effector-to-target ratios. These measurements provide time-resolved information on antigen-dependent cytotoxicity and spatial association during the observation period, supporting its potential utility as a preclinical platform for CAR T cell development and future personalized immunotherapy studies.
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