HPV 16 E5 oncoprotein is expressed in early stage carcinogenesis and can be a target of immunotherapy

F. Paolini, G. Curzio, M. N. Cordeiro, S. Massa, L. Mariani, F. Pimpinelli, A. C. de Freitas, R. Franconi, A. Venuti

Research output: Contribution to journalArticle

Abstract

HPV16 persistent infection is a well-known condition that precedes human cancer development. High risk HPV E5 proteins cooperate with E6/E7 oncogenes to promote hyper-proliferation of infected cells leading to possible cancer progression. Thus, presence of E5 viral transcripts could be a key marker of active infection and, in turn, a target of immunotherapy. Purpose of the study is to detect E5 transcripts in clinical samples and to explore the activity of novel anti-HPV16 E5 DNA vaccines. HPV transcripts were detected by PCR with specific primers encompassing the splice-donor sites of E5 transcript. For E5-based immunotherapies, 2 E5-based versions of DNA vaccines carrying whole E5 gene or a synthetic multiepitope gene were improved by fusion to sequence of PVX coat protein. These vaccines were challenged with a new luminescent animal model based on C3-Luc cell line. E5 transcripts were detected in clinical samples of women with HPV positive low-grade SIL, demonstrating the validity of our test. In C3 pre-clinical mouse model, vaccine candidates were able to induce a strong cellular immunity as indicated by ELISPOT assays. In addition, E5-CP vaccines elicited strong anti-tumor effects as showed by decreased tumor growth monitored by animal imaging. The tumor growth inhibition was comparable to those obtained with anti-E7 DNA vaccines. In conclusion, detection of E5 transcripts in clinical samples indicates that E5 is a possible target of immunotherapy. Data from pre-clinical model demonstrate that E5 genetic immunization is feasible, efficacious and could be utilized in clinical trials.
Original languageEnglish
Pages (from-to)291-297
Number of pages7
JournalHuman Vaccines and Immunotherapeutics
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

Keywords

  • E5
  • HPV
  • HPV transcripts
  • cancer
  • immunotherapy
  • therapeutic vaccine

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    Paolini, F., Curzio, G., Cordeiro, M. N., Massa, S., Mariani, L., Pimpinelli, F., Freitas, A. C. D., Franconi, R., & Venuti, A. (2017). HPV 16 E5 oncoprotein is expressed in early stage carcinogenesis and can be a target of immunotherapy. Human Vaccines and Immunotherapeutics, 13(2), 291-297. https://doi.org/10.1080/21645515.2017.1264777 [doi]