Novel Antigenic Targets of HPV Therapeutic Vaccines

Abstract

Human papillomavirus (HPV) infection is the cause of the majority of cervical cancers and head and neck cancers worldwide. Although prophylactic vaccines and cervical cancer screening programs have shown efficacy in preventing HPV-associated cervical cancer, cervical cancer is still a major cause of morbidity and mortality, especially in third world countries. Furthermore, head and neck cancer cases caused by HPV infection and associated mortality are increasing. The need for better therapy is clear, and therapeutic vaccination generating cytotoxic T cells against HPV proteins is a promising strategy. This review covers the current scene of HPV therapeutic vaccines in clinical development and discusses relevant considerations for the design of future HPV therapeutic vaccines and clinical trials, such as HPV protein expression patterns, immunogenicity, and exhaustion in relation to the different stages and types of HPV-associated lesions and cancers. Ultimately, while the majority of the HPV therapeutic vaccines currently in clinical testing target the two HPV oncoproteins E6 and E7, we suggest that there is a need to include more HPV antigens in future HPV therapeutic vaccines to increase efficacy and find that especially E1 and E2 could be promising novel targets.

Recurrent or primary metastatic cervical cancer: current and future treatments

“…72 Traditionally, CC has been the main focus for research on HPVassociated disease and development of prophylaxis and therapy against such. 73 ISA101, a synthetic long peptide of HPV16 E6 and E7 in combination with CT, was tested in 77 patients with advanced, metastatic, or recurrent CC. The treatment resulted in regression and SD, both in 43% of the patients.…”

“… 72 Traditionally, CC has been the main focus for research on HPV-associated disease and development of prophylaxis and therapy against such. 73 …”

Efficacy and Safety of Immunotherapy for Cervical Cancer—A Systematic Review of Clinical Trials

“…However, an ongoing trial IMMNUOCERV (NCT04580771) is currently assessing a liposomal HPV-16 E6/E7 multipeptide vaccine (PDS0101) combined with CRT in advanced cervical cancer patients. Overall, therapeutic vaccines are a growing and promising research trend in cancer therapy, with multiple ongoing clinical trials, especially for HPV-associated cancers, including head and neck cancers, cervical, vulva, vaginal or anal cancers [ 108 ].…”

The Role of Type-2 Conventional Dendritic Cells in the Regulation of Tumor Immunity

“…Topical treatment of GTL001 with TLR7/8 agonist eradicated HPV-16 E7-expressing cervical carcinoma in a mouse model [121]. However, no clinical difference was observed between therapy and placebo group in a phase II study of GTL001 with TLR7/8 agonist in women with HPV16 and/or 18 infection [122].…”