Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies

Abstract

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines

“…Even though theoretical possibility of integration into the host genome exists, they are generally considered safe. 13 In the present study, we evaluated the potential of using the PGIP ss in the context of DNA immunization to enhance immunity responses to the encoded E7 antigen. In our previous studies, mouse DNA immunization with E7 fused to PVX CP generated CD4C T cell responses that increased CD8C T cell priming through the presentation within MHC class II pathway.…”

Cervical cancer: A global health crisis

“…45 The 2 main oncogenes associated with HPV-driven cancers, E6 and E7, are considered to be excellent targets for immunotherapy.…”

Identificaiton of Novel Immunogenic Human Papillomavirus Type 16 E7-Specific Epitopes Restricted to HLA-A*33;03 for Cervical Cancer Immunotherapy

“…Several trials, involving peptide-protein-based vaccines and live-vector based vaccines, also demonstrated that these approaches are effective in cervical intraepithelial neoplasia (CIN) as well as in advanced cervical cancer (CC) patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease 25. The strength of the present study is the fact that identified HPV 16 E7 specific peptides could play an important role as a basic platform for both the development of peptide-induced CTL vaccines and development of peptide-based CTL immune monitoring system which are very specific for HLA-A33 cervical cancer patients in Korean and Asian peoples.…”