The Efficacy of Therapeutic DNA Vaccines Expressing the Human Papillomavirus E6 and E7 Oncoproteins for Treatment of Cervical Cancer: Systematic Review.

Ayazhan Akhatova,Chee Kai Chan,Azliyati Azizan,Gulzhanat Aimagambetova

doi:10.3390/vaccines10010053

Ayazhan Akhatova, Chee Kai Chan + Show 2 more

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https://doi.org/10.3390/vaccines10010053

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Abstract

Cervical cancer is recognized as a serious public health problem since it remains one of the most common cancers with a high mortality rate among women despite existing preventative, screening, and treatment approaches. Since Human Papillomavirus (HPV) was recognized as the causative agent, the preventative HPV vaccines have made great progress over the last few years. However, people already infected with the virus require an effective treatment that would ensure long-term survival and a cure. Currently, clinical trials investigating HPV therapeutic vaccines show a promising vaccine-induced T-cell mediated immune response, resulting in cervical lesion regression and viral eradication. Among existing vaccine types (live vector, protein-based, nucleic acid-based, etc.), deoxyribonucleic acid (DNA) therapeutic vaccines are the focus of the study, since they are safe, cost-efficient, thermostable, easily produced in high purity and distributed. The aim of this study is to assess and compare existing DNA therapeutic vaccines in phase I and II trials, expressing HPV E6 and E7 oncoproteins for the prospective treatment of cervical cancer based on clinical efficacy, immunogenicity, viral clearance, and side effects. Five different DNA therapeutic vaccines (GX-188E, VGX-3100, pNGVL4a-CRT/E7(detox), pNGVL4a-Sig/E7(detox)/HSP70, MEDI0457) were well-tolerated and clinically effective. Clinical implementation of DNA therapeutic vaccines into treatment regimen as a sole approach or in combination with conservative treatment holds great potential for effective cancer treatment.

Highlights

Cervical cancer is a largely preventable cancer of the cervix, which is the narrow part of the lower uterus that connects to the vagina
The aim of this article is to assess and compare existing deoxyribonucleic acid (DNA) therapeutic vaccines, which are evaluated in phase I and II trials, expressing Human Papillomavirus (HPV) E6 and E7 oncoproteins for the prospective treatment of cervical cancer based on clinical efficacy, immunogenicity, viral clearance, and side effects
From the remaining 37 articles, 24 articles were excluded at this stage: 11 studies were mouse model-based, 9 studies were not addressing the study question, 2 studies were regarding the preventative vaccines, and 2 studies included additional oncogenes in the development of therapeutic vaccines

Summary

Introduction

Cervical cancer is a largely preventable cancer of the cervix, which is the narrow part of the lower uterus that connects to the vagina. According to the World Health Organization (WHO) statistics, cervical cancer became the fourth most frequent cancer in women in 2018, with 570,000 cases, which represent 6.6% of all female cancers worldwide [1]. Cervical cancer is the 2nd most common type of cancer among females, and the 4th most common cause of cancer-related deaths (8.5%) among women in Kazakhstan [1]. Previous studies have established the strong causative association between persistent infection with certain high-risk Human Papillomavirus (HPV) types and the development of cervical cancer [2]. HPV is a small, non-enveloped deoxyribonucleic acid (DNA) tumor virus, which primarily affects human vaginal and oral mucosa [2].

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