title: Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas.
abstract: OBJECTIVE
  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 ((211)At-cMAb U36). Effects on (211)At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells.
  
  
  RESULTS
  Cetuximab in combination with (211)At-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 (211)At-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.
authors.affiliation: Unit of Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala, Sweden. marika.nestor@bms.uu.se
authors.forename: Marika
authors.initials: M
authors.lastname: Nestor
authors.forename: Magnus
authors.initials: M
authors.lastname: Sundström
authors.forename: Matti
authors.initials: M
authors.lastname: Anniko
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001246:Astatine / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D000068818:Cetuximab; D006801:Humans; D016499:Radioimmunotherapy / Q000379:methods*; D014410:Tumor Stem Cell Assay
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D001246:Astatine