Lung tumouroids 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 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.
Authors
- Dimitrios L. Wagner (ORCID: https://orcid.org/0000-0002-2189-3579)
- Claudia Vollbrecht (ORCID: https://orcid.org/0000-0002-0861-001X)
- Harald Stachelscheid (ORCID: https://orcid.org/0000-0002-9283-4605)
- Ansgar Petersen (ORCID: https://orcid.org/0000-0002-3075-4300)
- Andreas C. Hocke (ORCID: https://orcid.org/0000-0002-6935-8612)
- Samira Picht (ORCID: https://orcid.org/0000-0002-7761-5711)
- Julia K. Polansky (ORCID: https://orcid.org/0000-0003-4727-2540)
- Aron Elsner
- Anna Löwa (ORCID: https://orcid.org/0000-0002-5551-731X)
- Anke Sommerfeld
- Julia Strauchmann
- Simon Schallenberg (ORCID: https://orcid.org/0000-0002-7897-7116)
- Lukas Ehlen (ORCID: https://orcid.org/0000-0002-0820-6594)
- Sarah Schulenberg (ORCID: https://orcid.org/0000-0003-3719-6652)
- Janine Arndt (ORCID: https://orcid.org/0000-0001-5952-5096)
- Martí Farrera-Sal (ORCID: https://orcid.org/0000-0002-8170-1276)
- Regina Stark (ORCID: https://orcid.org/0000-0001-7693-799X)
- Franka Klatte‐Schulz (ORCID: https://orcid.org/0000-0001-6079-228X)
- Gabriela Korus
- Mingxing Yang
- Jens‐Carsten Rückert
- Marco Mai
- Rebecca Friedrich
- Daniel Geray
- Cedric Scholz
- Denise Treue
- Martin Szyska
- Jonas Kath
- Claudia Spies
- Valeria Fernandez Vallone
- Lena Peter
- Oliver Klein
- Michael Schmueck-Henneresse
- Maria Joosten
Institutions
- Baylor College of Medicine (US)
- Leibniz Association (DE)
- Humboldt-Universität zu Berlin (DE)
- German Rheumatism Research Centre (DE)
- Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Bayer (Germany) (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2026-01-21
- DOI
- https://doi.org/10.1038/s41551-025-01594-3
- Citations
- 1
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 24.20