Authors
Chiara Malinconico, Justus Weber, Antonina Jana Polzien, Agnes Bonifacius, Melina Umland, Quentin Deveuve, Tonia Bargmann, Katharina Zimmermann, Johanna Gellert, Lavinia Neubert, Stefan Dübel, Axel Schambach, Armin Braun, Rainer Blasczyk, Hinrich Abken, Michael Hudecek, Anna Christina Dragon, Britta Eiz-Vesper
Published in
Cancer immunology research. Sep 22, 2026. Epub Sep 22, 2026.
Abstract
To date, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide, underscoring the urgent need for new treatment options. The oncofetal carbohydrate CD176 is masked on healthy tissues but is present on a variety of cancer entities and is associated with cancer invasiveness and metastasis. In this study, we employed chimeric antigen receptor T cells (CAR-Ts) directed against CD176 for treatment of NSCLC. CD176-CAR-Ts were optimized with an additional inducible cassette encoding IL-18 (CD176-iIL18-TRUCKs) or IL-12 (CD176-iIL12-TRUCKs) to augment antitumor reactivity through autocrine and paracrine signaling. CD176-iIL18- and CD176-iIL12-TRUCKs eradicate NSCLC cells in a 3D tumor spheroid model and tissue slices derived from lung adenocarcinoma patients more potently than CD176-CAR-Ts. Administration of TRUCKs in a lung carcinoma xenograft mouse model results in partial or complete tumor eradication in all mice treated with CD176-iIL12-TRUCKs and in 50% of mice treated with CD176-iIL18-TRUCKs. This study highlights the potential of CD176 as a CAR-T-cell target and suggest CD176-CAR-Ts armored with IL-18 or IL-12 as promising new therapeutic approach for the treatment of NSCLC and several other CD176-positive cancer entities.
PMID:
42770707
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.
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