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Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Tolmachev)
2011 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 38, no 1, 103-112 p.Article in journal (Refereed) Published
Abstract [en]

Aim

The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed.

Methods

SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 (211At-cMAb U36). Effects on 211At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells.

Results

Cetuximab in combination with 211At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced 211At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR.

Conclusions

Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

Place, publisher, year, edition, pages
2011. Vol. 38, no 1, 103-112 p.
Keyword [en]
Alpha radiation, Astatine, Cetuximab, EGFR, Radioimmunotherapy, Squamous cell carcinoma
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:uu:diva-130150DOI: 10.1016/j.nucmedbio.2010.06.014ISI: 000286574800010PubMedID: 21220133OAI: oai:DiVA.org:uu-130150DiVA: diva2:346730
Available from: 2010-09-02 Created: 2010-09-02 Last updated: 2017-12-12Bibliographically approved

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Nestor, MarikaSundström, MagnusAnniko, MattiTolmachev, Vladimir

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