Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

Nestor, Marika; Sundström, Magnus; Anniko, Matti; Tolmachev, Vladimir

doi:10.1016/j.nucmedbio.2010.06.014

« Previous Next »Nuclear Medicine and Biology
Volume 38, Issue 1 , Pages 103-112, January 2011

Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

Marika Nestor
- Unit of Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala, Sweden
- Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala, Sweden
- Corresponding author. Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 85 Uppsala, Sweden. Tel.: +46 (0)18 471 3868; fax: +46 (0)18 471 3432.
Magnus Sundström
- Unit of Molecular Pathology, Department of Genetics and Pathology, Uppsala University, Sweden
Matti Anniko
- Unit of Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala, Sweden
Vladimir Tolmachev
- Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala, Sweden

Received 16 April 2010; received in revised form 15 June 2010; accepted 18 June 2010. published online 18 August 2010.

Abstract

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.

Keywords: Cetuximab, EGFR, Squamous cell carcinoma, Astatine, Alpha radiation, Radioimmunotherapy