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

TitleHPV 16 E5 oncoprotein is expressed in early stage carcinogenesis and can be a target of immunotherapy
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2017
AuthorsPaolini, F., Curzio G., Cordeiro M.N., Massa Silvia, Mariani L., Pimpinelli F., de Freitas A.C., Franconi Rosella, and Venuti A.
JournalHuman Vaccines and Immunotherapeutics
Keywordsanimal, animal cell, animal model, Animals, antineoplastic activity, article, biosynthesis, C57BL mouse, cancer immunotherapy, cancer inhibition, CD4+ T lymphocyte, CD8+ T lymphocyte, Cellular, cellular immunity, coat protein, complication, DNA, DNA vaccine, drug targeting, enzyme linked immunospot assay, Enzyme-Linked Immunospot Assay, epitope, Female, Flow cytometry, gamma interferon, human, Human papillomavirus type 16, Humans, immune response, Immunity, immunotherapy, Inbred C57BL, Mice, mouse, nonhuman, oncogene protein E5, Oncogene Proteins, oncoprotein, papillomavirus infection, Papillomavirus Infections, Papillomavirus Vaccines, Pathology, procedures, real time polymerase chain reaction, reverse transcription polymerase chain reaction, spleen cell, treatment outcome, Uterine Cervical Neoplasms, Vaccines, Viral, Wart virus vaccine

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. © 2017 Taylor & Francis.


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Citation KeyPaolini2017291