title: Combined treatment of the experimental human papilloma virus-16-positive cervical and head and neck cancers with cisplatin and radioimmunotherapy targeting viral E6 oncoprotein.
abstract: BACKGROUND
  Human papilloma virus (HPV) is implicated in >99% of cervical cancers and ∼40% of head and neck squamous cell carcinoma (HNSCC). We previously targeted E6 oncogene with (188)Rhenium-labelled monoclonal antibody (mAb) C1P5 to HPV16 E6 in cervical cancer and HNSCC. Intranuclear E6 can be accessed by mAbs in non-viable cells with leaky membranes. As radioimmunotherapy (RIT) efficacy depends on the availability of target protein-we hypothesised that pretreatment with cisplatin will kill some tumour cells and increase E6 availability for RIT.
  
  
  METHODS
  Mice with subcutaneous HPV16+ cervical (CasKi) and HNSCC (2A3) tumours were pretreated with 0-7.5 mg kg(-1) per day cisplatin for 3 days followed by (188)Re-C1P5 and biodistribution was performed 24 h later. For RIT, the animals were treated with: 5 mg kg(-1) per day cisplatin for 3 days; or 5 mg kg(-1) per day cisplatin for 3 days followed 200 or 400μCi (188)Re-C1P5 mAb; or 200 or 400μCi (188)Re-C1P5 mAb; or left untreated, and observed for tumour growth for 24 days.
  
  
  RESULTS
  Pretreatment with cisplatin increased the uptake of (188)Re-C1P5 in the tumours 2.5 to 3.5-fold and caused significant retardation in tumour growth for CasKi and 2A3 tumours in both RIT alone and cisplatin, and RIT groups in comparison with the untreated control and cisplatin alone groups (P<0.05). The combined treatment was more effective than either modality alone (P<0.05).
  
  
  CONCLUSIONS
  Our study demonstrates that preceding RIT targeting E6 oncogene with chemotherapy is effective in suppressing tumour growth in mouse models of HPV16+ cancers.
authors: Department of Radiology, Albert Einstein College of Medicine, 1695A Eastchester Road, Bronx, NY 10461, USA.
authors: M
authors: M
authors: Harris
authors: X G
authors: XG
authors: Wang
authors: Z
authors: Z
authors: Jiang
authors: R
authors: R
authors: Phaeton
authors: W
authors: W
authors: Koba
authors: G L
authors: GL
authors: Goldberg
authors: A
authors: A
authors: Casadevall
authors: E
authors: E
authors: Dadachova
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000628:therapy* / Q000821:virology*; D052162:Human papillomavirus 16 / Q000254:growth & development*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D016499:Radioimmunotherapy / Q000379:methods*; D011877:Radionuclide Imaging; D012097:Repressor Proteins / Q000276:immunology*; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D002945:Cisplatin
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