Therapeutic virus-like particle- based vaccines against cervical cancer
Cervical cancer represents the second most frequent gynecological malignancy in the world. It is caused by a persistent virus infection by the high-risk human papillomavirus (HR-HPV) but no cervical cancer vaccine has been marketed to date. In a paper published in PLoS, Juan Martin Caballero, director of the PRBB animal facility, together with colleagues from a pharmaceutical company have generated a virus-like particle (VLP)-based vaccine to treat this cancer and have tested it in humanized transgenic mice.
The researchers took a long C-terminal fragment of the HPV-16 E7 protein – one of the two viral proteins necessary for induction and maintenance of malignant transformation – and introduced it into the infectious bursal disease virus (IBDV) VLP. The combination of tumor antigens and IBDV-VLPs has been shown as a good strategy to boost the immune response and direct it against different types of cancer.
The authors tested the therapeutic potential of their new vaccine, VLP-E7, in HLA-A2 humanized transgenic mice grafted with TC1/A2 tumor cells. They performed a series of tumour challenge experiments demonstrating a strong immune response against already formed tumors, including its complete eradication. Remarkably, therapeutic efficacy was obtained with a single dose without adjuvant and it persisted when the mice were re-challenged with a second tumor cell inoculation. As the authors state, this indicates a high immunogenic potential and in vivo efficacy of their cervical cancer candidate vaccine, VLP-E7, although further studies will be necessary to investigate the potential of the IBDV VLP carrier and its applications to other human diseases.
Martin Caballero J, Garzón A, González-Cintado L, Kowalczyk W, Jimenez Torres I, Calderita G, Rodriguez M, Gondar V, Bernal JJ, Ardavín C, Andreu D, Zürcher T, von Kobbe C. Chimeric Infectious Bursal Disease Virus-Like Particles as Potent Vaccines for Eradication of Established HPV-16 E7-Dependent Tumors. PLoS One. 2012;7(12):e52976