Lung tumoroids as a testing platform for precision CAR T-cell therapy

Lung cancer, the leading cause of cancer-related mortality, presents major challenges for both standard-of-care therapies and innovative treatments like CAR T cells due to tumor heterogeneity and resistance. To aid in personalized treatment decisions, preclinical models that incorporate these patient-specific factors are essential. In this study, we developed a platform using matched lung tumoroids and healthy lung organoids. The tumoroids retained the identity of the original tumors, as confirmed by genomic, epigenomic, histological, and proteomic analyses. These tumoroids accurately replicated individual patient responses to standard-of-care therapies, highlighting their predictive value. Our platform enabled the identification of individual responses to CAR T cells and associated mechanisms, indicating that efficacy may be influenced by immunoregulatory factors such as autophagy, IL-8 secretion, and PDL1 overexpression. Our modeling strategy shows promise for guiding patient-specific treatment decisions and may facilitate the preselection of lung cancer patients for CAR T-cell therapy.