Development of dendritic cell-based vaccines against HPV – associated malignancies

In several types of human tumours a close association with oncogenic viruses has been established. Animal models mimicking these tumours with regard to their aetiology and expression of virus-related molecules have been developed. The rationale for development of the animal models was to create experimental systems allowing us to compare the efficacy of different therapeutic protocols, with the final aim to optimize these therapeutic procedures prior to clinical trials. Cervical carcinomas (CC) represent one of the aforementioned human oncogenic virus-associated tumour types. High-risk human papilloma viruses (HPV), particularly HPV 16, 18, 31, 33, 45, and 56, are associated with nearly one hundred percent of CC. TC-1 (MHC class I+) and MK16 (MHC class I-), established and transplantable cell lines in syngeneic C57BL/6 mice which mimicking human HPV 16associated neoplams were utilized to investigate the efficacy of DC-based vaccines against HPV-associated tumours in preclinical studies. We have found that the sc administration of bone marrow-derived dendritic cells (BMDC) vaccines at the site of subsequent MK16 challenge or in 5-day sc tumours inhibited growth of the TC-1 and MK16 tumour transplants and its lung metastasis. In a clinically more relevant setting, mice with surgical minimal residual tumour TC-1 disease were treated with pulsed BMDC. The administration of those DC preparations at the site of surgery significantly inhibited the growth of recurrent tumours. A significant reduction of the tumour growth was observed in groups treated with terminally differentiated BMDC pulsed with the antigen in the form of TC-1 lysate, as well as co-cultured with irradiated TC-1 cells, as compare as compared to the operated control groups. In summary, we have investigated the capacity of cellular vaccines based on dendritic cells loaded with human HPV 16 oncoproteinantigens induce immune responses to elicit protective immunity in a murine experimental model mimicking human HPV16-associated carcinomas. These results can be used as a basis for translatable research in clinical trials investigating DC-based vaccines against CC.