Language

English

Publication Date

4-1-2026

Journal

Nature Biomedical Engineering

DOI

10.1038/s41551-025-01594-3

PMID

41565786

PMCID

PMC13099645

PubMedCentral® Posted Date

1-21-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Lung cancer, the leading cause of cancer-related mortality, presents major challenges for both standard therapies and chimeric antigen receptor (CAR) T cell therapy due to tumour heterogeneity and resistance. Preclinical models that capture patient-specific factors are essential for personalizing treatment decisions. Here we show that matched lung tumouroids and healthy lung organoids derived from patients provide a robust platform for studying therapy responses. The tumouroids faithfully retained the molecular and histological identity of the original tumours, as confirmed by genomic, epigenomic and proteomic analyses, and accurately replicated individual patient responses to standard-of-care therapies. Importantly, the platform also revealed patient-specific CAR T cell responses, uncovering a complex interplay between target antigen density and broader, tumour-intrinsic resistance programmes. By capturing these individualized factors, our model supports rational patient selection for CAR T cell therapy in lung cancer and provides a framework for designing CAR T cells tailored to overcome resistance mechanisms in solid tumours.

Keywords

Humans, Lung Neoplasms, Immunotherapy, Adoptive, Receptors, Chimeric Antigen, Animals, T-Lymphocytes, Precision Medicine, Lung, Proteomics, Cell Line, Tumor, Cancer, Cancer models, Immunotherapy

Published Open-Access

yes

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