Therapeutic dendritic cell vaccination with Ag coupled to cholera toxin in combination with intratumoural CpG injection leads to complete tumour eradication in mice bearing HPV 16 expressing tumours

Abstract

We have evaluated whether cholera toxin (CT) can enhance the efficiency of therapeutic dendritic cell (DC) vaccination in mice bearing a human papilloma virus (HPV) 16 antigen (Ag) expressing tumour. Mice were therefore injected with the TC-1 cancer cell line expressing E6 and E7, which are the major oncogenic proteins produced in HPV-induced cervical cancer, and they were then vaccinated with Ag pulsed DCs. While vaccination with E7 pulsed DCs had no impact on tumour growth, DCs pulsed with CT conjugated E7 (CT-E7) significantly reduced tumour size. However, this treatment was only able to eradicate the tumour in 11% of the affected animals. For complete tumour eradication, combinational therapy with CT-E7 pulsed DCs and local treatment of the tumour with CpG oligodeoxynucleotides (CpG) was required. Combinational therapy was associated with increased expression of MHC I and MHC II and increased levels of chemokine production in the tumour. These results suggest that combined treatment with CT-Ag pulsed DCs and local CpG administration offers an efficient strategy to eradicate an already existing HPV-E7 expressing tumour in mice.