Therapeutic cancer vaccines targeting viral antigens

Promising results have been obtained with therapeutic vaccines against diseases caused by Epstein–Barr virus (EBV) and high-risk human papilloma virus (HPV). However, so far none of these efforts has led to market approval of registered therapeutic vaccines against these agents or diseases caused by them, nor against persistent infection or neoplastic diseases caused by human T-cell lymphotropic virus type 1 (HTLV-1), hepatitis B virus (HBV), hepatitis C virus (HCV), or Merkel carcinoma virus. Persistent HCV infection and some cancers caused by EBV can be effectively treated with antiviral agents or immunotherapy. EBV-induced Hodgkin’s disease and skin cancers caused by Merkel carcinoma virus respond well to treatment with anti-PD-(L)1 checkpoint blockers. With the exception of these therapies, there is a great medical need for therapeutic vaccines eliciting robust T-cell responses against most EBV-induced cancers, in particular, nasopharyngeal carcinoma and against persistent infections and (pre-)malignant disease caused by HTLV I, HBV, high-risk HPV, and Merkel Carcinoma virus. Optimal development of therapeutic vaccines against these viruses and virus-induced (pre-)malignant diseases has to reckon with the intricate immunosuppressive and evasive mechanisms of the viruses themselves as well as with the need for cotreatment to combat the hostile tumor microenvironment and generalized immunosuppression associated with late-stage cancer. Attractive co-treatments with therapeutic vaccines are some forms of chemotherapy and PD-(L)1 T-cell checkpoint blockers.