title: Combined treatment of the immunoconjugate bivatuzumab mertansine and fractionated irradiation improves local tumour control in vivo.
abstract: OBJECTIVE
  To test whether BIWI 1 (bivatuzumab mertansine), an immunoconjugate of the humanized anti-CD44v6 monoclonal antibody BIWA 4 and the maytansinoid DM1, given simultaneously to fractionated irradiation improves local tumour control in vivo compared with irradiation alone.
  
  
  METHODS
  For growth delay, FaDu tumours were treated with 5 intravenous injections (daily) of phosphate buffered saline (PBS, control), BIWA 4 (monoclonal antibody against CD44v6) or BIWI 1 (bivatuzumab mertansine) at two different dose levels (50 μg/kg DM1 and 100 μg/kg DM1). For local tumour control, FaDu tumours received fractionated irradiation (5f/5d) with simultaneous PBS, BIWA 4 or BIWI 1 (two dose levels).
  
  
  RESULTS
  BIWI 1 significantly improved local tumour control after irradiation with 5 fractions already in the lower concentration. The dose modifying factor of 1.9 is substantial compared to the majority of other modifiers of radiation response.
  
  
  CONCLUSIONS
  Because of the magnitude of the curative effect, this approach is highly promising and should be further evaluated using similar combinations with improved tumour-specificity.
authors.affiliation: Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Technische Universität, Dresden, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Gurtner
authors.forename: Franziska
authors.initials: F
authors.lastname: Hessel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eicheler
authors.forename: Annegret
authors.initials: A
authors.lastname: Dörfler
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Heider
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000628:therapy*; D008297:Male; D008453:Maytansine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D047368:Tumor Burden
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C519271:bivatuzumab mertansine; D008453:Maytansine