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 188Rhenium-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.MethodsMice 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 188Re-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 188Re-C1P5 mAb; or 200 or 400μCi 188Re-C1P5 mAb; or left untreated, and observed for tumour growth for 24 days.Results:Pretreatment with cisplatin increased the uptake of 188Re-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).Conclusion:Our study demonstrates that preceding RIT targeting E6 oncogene with chemotherapy is effective in suppressing tumour growth in mouse models of HPV16+ cancers.