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

Vaccines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 53
Author(s):  
Ayazhan Akhatova ◽  
Chee Kai Chan ◽  
Azliyati Azizan ◽  
Gulzhanat Aimagambetova

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.

Open Biology ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. 170111 ◽  
Author(s):  
Diego Carrillo ◽  
Juan P. Muñoz ◽  
Hernán Huerta ◽  
Gabriel Leal ◽  
Alejandro Corvalán ◽  
...  

The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells. The PIR expression was dependent on functional HR-HPV E6 and E7 oncoproteins even though the E7 oncoprotein had higher activity to induce PIR overexpression in comparison with E6. In addition, using an siRNA for PIR silencing in oral cells ectopically expressing HR-HPV E6/E7, there was a significant increase in E-cadherin transcripts and a decrease in Vimentin, Slug, Zeb and Snail transcripts, suggesting that HR-HPV-induced PIR overexpression is involved in epithelial–mesenchymal transition. Furthermore, migration of PIR-silenced cells was significantly decreased. Finally, using inhibitors of some specific pathways, it was found that EGFR/ERK and PI3 K/AKT signalling pathways are important for E7-mediated PIR overexpression. It can be concluded that PIR gene expression is highly dependent on the expression of HR-HPV oncoproteins and is important for EMT regulation.


1994 ◽  
Vol 137 (3-4) ◽  
pp. 341-353 ◽  
Author(s):  
I. Nindl ◽  
L. Benitez-Bribiesca ◽  
J. Berumen ◽  
N. Farmanara ◽  
S. Fisher ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Joseph M. Bay ◽  
Bruce K. Patterson ◽  
Nelson N. H. Teng

The constitutive proliferation and resistance to differentiation and apoptosis of neoplastic cervical cells depend on sustained expression of human papillomavirus oncogenes. Inhibition of these oncogenes is a goal for the prevention of progression of HPV-induced neoplasias to cervical cancer. SiHa cervical cancer cells were transfected with an HPV-16 promoter reporter construct and treated with leukemia inhibitory factor (LIF), a human cytokine of the interleukin 6 superfamily. SiHa and CaSki cervical cancer cells were also assessed for proliferation by MTT precipitation, programmed cell death by flow cytometry, and HPV E6 and E7 expression by real-time PCR. LIF-treated cervical cancer cells showed significantly reduced HPV LCR activation, reduced levels of E6 and E7 mRNA, and reduced proliferation. We report the novel use of LIF to inhibit viral oncogene expression in cervical cancer cells, with concomitant reduction in proliferation suggesting re-engagement of cell-cycle regulation.


2019 ◽  
Vol 12 (10) ◽  
pp. 1289-1295 ◽  
Author(s):  
Zewei Jiang ◽  
Joseph Albanese ◽  
Joshua Kesterson ◽  
Joshua Warrick ◽  
Rouzan Karabakhtsian ◽  
...  

2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.


2006 ◽  
Vol 19 (3) ◽  
pp. 468-480 ◽  
Author(s):  
Oscar Peralta-Zaragoza ◽  
Víctor Bermúdez-Morales ◽  
Lourdes Gutiérrez-Xicotencatl ◽  
Juan Alcocer-González ◽  
Félix Recillas-Targa ◽  
...  

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