title: Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors.
abstract: Cervical cancer is caused by persistent high-risk human papillomavirus (HR-HPV) infection and represents the second most frequent gynecological malignancy in the world. The HPV-16 type accounts for up to 55% of all cervical cancers. The HPV-16 oncoproteins E6 and E7 are necessary for induction and maintenance of malignant transformation and represent tumor-specific antigens for targeted cytotoxic T lymphocyte-mediated immunotherapy. Therapeutic cancer vaccines have become a challenging area of oncology research in recent decades. Among current cancer immunotherapy strategies, virus-like particle (VLP)-based vaccines have emerged as a potent and safe approach. We generated a vaccine (VLP-E7) incorporating a long C-terminal fragment of HPV-16 E7 protein into the infectious bursal disease virus VLP and tested its therapeutic potential in HLA-A2 humanized transgenic mice grafted with TC1/A2 tumor cells. We performed a series of tumor challenge experiments demonstrating a strong immune response against already-formed tumors (complete eradication). Remarkably, therapeutic efficacy was obtained with a single dose without adjuvant and against two injections of tumor cells, indicating a potent and long-lasting immune response.
authors.affiliation: Laboratory Animal Unit, Barcelona Biomedical Research Park, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Martin Caballero
authors.forename: Ana
authors.initials: A
authors.lastname: Garzón
authors.forename: Leticia
authors.initials: L
authors.lastname: González-Cintado
authors.forename: Wioleta
authors.initials: W
authors.lastname: Kowalczyk
authors.forename: Ignacio
authors.initials: I
authors.lastname: Jimenez Torres
authors.forename: Gloria
authors.initials: G
authors.lastname: Calderita
authors.forename: Margarita
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Virgínia
authors.initials: V
authors.lastname: Gondar
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Bernal
authors.forename: Carlos
authors.initials: C
authors.lastname: Ardavín
authors.forename: David
authors.initials: D
authors.lastname: Andreu
authors.forename: Thomas
authors.initials: T
authors.lastname: Zürcher
authors.forename: Cayetano
authors.initials: C
authors.lastname: von Kobbe
mesh_terms: D000818:Animals; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D007243:Infectious bursal disease virus / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle; C059731:oncogene protein E7, Human papillomavirus type 16