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: Juan Martin Caballero, Ana Garzón, Leticia González-Cintado, Wioleta Kowalczyk, Ignacio Jimenez Torres, Gloria Calderita, Margarita Rodriguez, Virgínia Gondar, Juan Jose Bernal, Carlos Ardavín, David Andreu, Thomas Zürcher, Cayetano von Kobbe
• Journal: PloS one (PLoS One) Vol. 7 Issue 12 Pg. e52976 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23300838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Papillomavirus E7 Proteins
• Papillomavirus Vaccines
• Vaccines, Virus-Like Particle
• oncogene protein E7, Human papillomavirus type 16

Topics

• Animals
• Female
• Human papillomavirus 16 (immunology)
• Infectious bursal disease virus (immunology)
• Mice
• Mice, Transgenic
• Papillomavirus E7 Proteins (immunology)
• Papillomavirus Infections (immunology, therapy)
• Papillomavirus Vaccines (immunology, therapeutic use)
• Uterine Cervical Neoplasms (immunology, therapy, virology)
• Vaccines, Virus-Like Particle (immunology, therapeutic use)