Human Papillomavirus: A Review of DNA based Therapeutic Cancer Vaccines Routes of Administration

Open Access

Year : 2021 | Volume : | Issue : 1 | Page : 5-13
By

    Chelsea Elwood

  1. Nicole Heck

  2. Chad Evans

  3. Joe Newtoff

  4. Kevin Schubach

  1. Assistant Professor, Department of Applied Medicine and Rehabilitation, Indiana State University, Terre Haute, Indiana, United States
  2. Associate Professor, Department of Applied Medicine and Rehabilitation, Indiana State University, Terre Haute, Indiana, United States
  3. Student, Department of Applied Medicine and Rehabilitation, Indiana State University, Terre Haute, Indiana, United States
  4. Student, Department of Applied Medicine and Rehabilitation, Indiana State University, Terre Haute, Indiana, United States
  5. Student, Department of Applied Medicine and Rehabilitation, Indiana State University, Terre Haute, Indiana, United States

Abstract

Human Papillomavirus is the most common sexually transmitted infection. While the virus can cause many negative health effects in both males and females, the most concerning and common of these is cervical cancer in females. Immunization is not effective in clearing HPV infection that is already present. Therefore, there is a need for therapeutic vaccines that work to combat the virus in an individual who has already been exposed and has a persistent infection causing cervical cancer. This paper reviews the literature on DNA vaccines and the success in eliminating cervical cancer cells by examining the route of administration. The most successful methods stimulated innate immune responses required to trigger strong and lasting adaptive immune responses. Currently, the best studies focus on gene gun, electroporation, tattooing, and microspheres/nanodelivery. Electroporation has the best results and is slightly more efficacious than the gene gun due to a small advantage in tumor reduction and the presence of larger human sample sizes. Microspheres show promise as well but require more research. The most common limitation of these methods is lack of human trials. The data that has been gathered so far is promising, though, and in the future, it could be groundbreaking in the treatment of cervical cancer due to persistent oncogenic HPV infection.

Keywords: Administration, cervical cancer, dendritic cells, HPV, vaccines

[This article belongs to International Journal of Immunological Nursing(ijin)]

How to cite this article: Chelsea Elwood, Nicole Heck, Chad Evans, Joe Newtoff, Kevin Schubach Human Papillomavirus: A Review of DNA based Therapeutic Cancer Vaccines Routes of Administration ijin 2021; 7:5-13
How to cite this URL: Chelsea Elwood, Nicole Heck, Chad Evans, Joe Newtoff, Kevin Schubach Human Papillomavirus: A Review of DNA based Therapeutic Cancer Vaccines Routes of Administration ijin 2021 {cited 2021 Feb 14};7:5-13. Available from: https://journals.stmjournals.com/ijin/article=2021/view=92118

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References

1. Cheng, M.A., Farmer, E., Huang, C., Lin, J., Hung, C.F., & Wu, T.C. (2018). Therapeutic DNA Vaccines for Human Papillomavirus and Associated Diseases. Hum Gene Ther, 29(9),971-996. doi:10.1089/hum.2017.197
2. Pokorna, D., Rubio I., & Muller M. DNA-vaccination via tattooing induces stronger humoral and cellular immune responses than intramuscular delivery supported by molecular adjuvants. Genet Vaccines Ther, 2008;6(4).
3. Gopee, N.V., Cui Y., Olson G., et al. Response of mouse skin to tattooing: use of SKH-1 mice as a surrogate model for human tattooing. Toxicology and Applied Pharmacology. 2005;209(2):145-158
4. Pokorna D., Polakova I., Kindlova, M., et al. Vaccination with human papillomavirus type 16-derived peptides using a tattoo device. Vaccine. 2009;27(27),3519-3529
5. Van den Berg J.H., Nujien B., Beijnen J.H., et al. Optimization of intradermal vaccination by DNA tattooing in human skin. Hum Gene Ther.2009; 20(3): 181-189
6. Van de Wall S., Walczak M., van Rooij N., et al. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7. Vaccines (Basel). 2015;3(2):221-238.
7. Chen C.H., Ji H., Suh K.W., et al. Gene gun-mediated DNA vaccination induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the liver and lungs. Gene Ther. 1999;6(12):1972-1981.
8. Gurunathan S., Klinman D.M., & Seder R. A. DNA vaccines: immunology, application, and optimization. Annu Rev Immunol.2000;18: 927-974.
9. Trimble C., Lin C.T., Hung C.F., et al. Comparison of the CD8+ T cell responses and antitumor effects generated by DNA vaccine administered through gene gun, biojector, and syringe. Vaccine.2003;21(25-26):4036-4042
10. Garza-Morales R., Perez-Trujillo J.J., Martinez-Jaramillo E., et al. A DNA Vaccine Encoding SA-4-1BBL Fused to HPV-16 E7 Antigen Has Prophylactic and Therapeutic Efficacy in a Cervical Cancer Mouse Model. Cancers (Basel).2019;11(1).
11. Alvarez R.D., Huh W.K., Bae S., et al. A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3). Gynecol Oncol.2016;140(2):245-252.
12. Smahel M., Polakova I., Duskova M., et al. The effect of helper epitopes and cellular localization of an antigen on the outcome of gene gun DNA immunization. Gene Ther.2014;21(2):225-232
13. Best S.R., Peng S., Juang C.M., et al. Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery. Vaccine.2009; 27(40):5450-5459
14. Gothelf A., Gehl J. What you always needed to know about electroporation based DNA vaccines. Hum Vaccin Immunother.2012;8(11):1694-1702.
15. Sales N.S., Silva J.R., Aps L., et al. In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8(+) T cells. Vaccine.2017;35(52):7240-7249.
16. Best S.R., Peng S., Juang C.M., et al. Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery. Vaccine.2009;27(40):5450-5459.
17. Kim T.J., Jin H.T., Hur S.Y., et al. Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nat Commun.2014;5:5317
18. Bagarazzi M.L., Yan J., Morrow M.P., et al. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med. 2012;4(155):155ra138.
19. Trimble C.L., Morrow M.P., Kraynyak K.A., et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet.2015;386(10008):2078-2088
20. Suschak J.J., Williams J.A., Schmaljohn C.S. Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity. Hum Vaccin Immunother.2017;13(12):2837-2848. doi:10.1080/21645515.2017.1330236
21. Saade, F., Petrovsky, N. Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines.2012;11(2):189-209
22. Morrow M.P., Kraynyak K.A., Sylvester A.J., et al. Clinical and Immunologic Biomarkers for Histologic Regression of High-Grade Cervical Dysplasia and Clearance of HPV16 and HPV18 after Immunotherapy. Clin Cancer Res.2018;24(2):276-294
23. Vici P., Mariani L., Pizzuti L., et al. Immunologic treatments for precancerous lesions and uterine cervical cancer. J Exp Clin Cancer Res.2014;33(29).


Regular Issue Open Access Article
Volume 7
Issue 1
Received October 27, 2020
Accepted December 21, 2020
Published February 14, 2021