Lentiviral-mediated panErbB CAR-T cell therapy against head and neck squamous cell carcinomas for patients with Fanconi anemia
Fanconi anemia (FA) is a DNA repair syndrome characterized by bone marrow failure and cancer predisposition, including acute myeloid leukemia and solid tumors such as head and neck squamous cell carcinoma (HNSCC). Due to the exacerbated toxicity of radio-chemotherapy in FA patients with HNSCC, there is an urgent need of safer and more efficient antitumoral therapies for these patients, such as those based on chimeric antigen receptor (CAR)-T cells. Here, we show that HNSCC cell lines from both the general population and patients with FA express ErbB family members, which can be recognized by the T1E panErbB ligand. The generation of a lentiviral vector encoding for a second-generation T1E-CAR allowed us to generate panErbB CAR-T cells from healthy donors (HDs) and patients with FA. Despite the molecular and cellular defects characteristic of FA cells, a similar efficacy of CAR-T generation was observed, regardless of the donor origin. In all cases, panErbB CAR-T cells exerted potent cytotoxicity against all HNSCC cell lines tested <i>in vitro</i>. In addition, intratumoral administration of these CAR-T cells in HNSCC xenografts markedly reduced tumor growth. These preclinical results suggest that panErbB CAR-T cells would represent a safe, non-genotoxic therapy for HNSCC, with particular applicability for patients with FA.
Authors
- Ángeles Juarranz (ORCID: https://orcid.org/0000-0002-6574-2887)
- Begoña Díez (ORCID: https://orcid.org/0000-0003-0083-1034)
- Juan A. Bueren (ORCID: https://orcid.org/0000-0002-3228-7013)
- Ricardo Errazquin
- Andrea V. Lopez (ORCID: https://orcid.org/0000-0002-0944-0710)
- David Charbonnier (ORCID: https://orcid.org/0000-0002-4865-3495)
- Corina Lorz (ORCID: https://orcid.org/0000-0001-8214-9076)
- Paula Vela (ORCID: https://orcid.org/0000-0002-4006-4645)
- Ramón Garcı́a-Escudero (ORCID: https://orcid.org/0000-0001-5640-6542)
- Omaira Alberquilla (ORCID: https://orcid.org/0000-0002-0301-8340)
- Sonia Del Marro (ORCID: https://orcid.org/0000-0002-3214-2615)
- John Maher (ORCID: https://orcid.org/0000-0001-8275-8488)
- Paula Rı́o (ORCID: https://orcid.org/0000-0002-5424-5543)
- Rebeca Sánchez‐Domínguez (ORCID: https://orcid.org/0000-0002-2073-2810)
- Beatriz Martín-Antonio (ORCID: https://orcid.org/0000-0003-0612-2693)
- José Antonio Casado (ORCID: https://orcid.org/0000-0003-2479-1508)
- Judith Balmañà (ORCID: https://orcid.org/0000-0002-0762-6415)
- Andrea Pascual
- Andrea Barahona
- Esperanza Esquinas
- M.Jordi Minguillón (ORCID: https://orcid.org/0000-0003-2124-8294)
Institutions
- Guy's Hospital (GB)
- King's College London (GB)
- Cell Therapy Catapult (GB)
- Instituto de Salud Carlos III (ES)
- Research Institute Hospital 12 de Octubre (ES)
- Escuela Nacional de Sanidad (ES)
- Eastbourne District General Hospital (GB)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (ES)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- Molecular Therapy Oncology
- Published
- 2025-09-23
- DOI
- https://doi.org/10.1016/j.omton.2025.201060
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Centro de Investigación Biomédica en Red de Cáncer
- Instituto de Salud Carlos III
- European Regional Development Fund
- Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas