Immunotherapy for Cervical Cancer

Abstract

The high-risk types of human papillomavirus (HPV) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. Despite recent advances in preventive HPV vaccine development, such preventive vaccines are unlikely to reduce the prevalence of HPV infections within the next few years, due to their cost and limited availability in developing countries. Furthermore, preventive HPV vaccines may not be capable of treating established HPV infections and HPV-associated lesions, which account for high morbidity and mortality worldwide. Thus, it is important to develop therapeutic HPV vaccines for the control of existing HPV infection and associated malignancies. Therapeutic vaccines are quite different from preventive vaccines in that they require the generation of cell-mediated immunity, particularly T cell-mediated immunity, instead of the generation of neutralizing antibodies. The HPV-encoded early proteins, E6 and E7 oncoproteins, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated cervical cancer and its precursor lesions and thus play crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover the various therapeutic HPV vaccines for cervical cancer, including live vector-based, peptide or protein-based, nucleic acid-based, and cell-based vaccines targeting the HPV E6 and/or E7 antigens. Furthermore, we will review the studies using therapeutic HPV vaccines in combination with other therapeutic modalities and review the latest clinical trials on therapeutic HPV vaccines.

Immunotherapy in new pre-clinical models of HPV-associated oral cancers

“…In spite of that, promising pre-clinical data have led to therapeutic vaccine candidates that are now in early phase clinical trials. 13 In our laboratories different HPV immunotherapeutic approaches were developed exploiting plants as bio-factories and as a source of immune-stimulators. Plant production of candidate prophylactic and therapeutic HPV vaccines is proven, with evidence of efficacy in animals.…”

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

“…A virus can deliver gene products directly into cells and because an active viral infection takes place, the immune system responds beter activating the cellular efector functions. The highly atenuated poxvirus strain modiied vaccinia virus Ankara (MVA) has become the vector of choice for novel HPV therapeutic vaccines [112]. This MVA virus is a non-replicating derivative from the virus of the smallpox vaccine.…”

Pathogen-Driven Cancers and Emerging Immune Therapeutic Strategies

“…10, 11). Another antiviral strategy, currently being tested in clinical trials for HPV treatment, is the use of therapeutic vaccines, which can range from peptide, protein, DNA, RNA, and dendritic cell–based vectors (12). For the nonviral pathogens, several antimicrobial therapies have been successfully used such as the quadruple therapy approach for H. pylori (a proton pump inhibitor, dual antibiotics, and bismuth) and praziquantel for the oncogenic parasites (13–15).…”