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
Juan Martín-Caballero at the Barcelona Biomedical Research Park animal facilities – Photo: © Diario Médico
The zebrafish (Danio rerio) is frequently used in drug discovery and key aspects of developmental biology. Mostly because of its quick development time (its organs are fully formed after just 48 hours) and transparent embryos. Above all, in research into regenerative medicine, because the fish is able to regenerate part of its caudal fin or, even, more than half of its heart. One of the main lines of research carried out with this animal model is that to discover the genes involved in regenerative processes. Several researchers at the PRBB have recently published work related to this topic in important scientific journals.
At the PRBB facilities, we have dozens of different strains of this fish, with 4,500 aquariums that can hold 50,000 adult fish. Hundreds of mutations of this species have already been created to study multiple human and animal illnesses, as it can be genetically modified easily and in a short time, only a few weeks, the effects of the genetic modification or chemical compound in question can be seen. As fertilization in this species is external, it isn’t necessary to euthanize the female in order to extract the embryos like in rodents.
The US FDA has calculated that up to $100 millions could be saved in drug discovery costs if the initial screening to select possible molecules was carried out on zebrafish embryos. This small fish, which measures only three or four centimeters in length at the adult stage, makes a great animal model, laying some 200 eggs per week. Its social impact is much lower as an animal model for biomedical and biotechnology research, and from a legal standpoint the use of embryos from this fish, which is less than five days old, isn’t subject to the European regulations that apply to any vertebrate used for scientific research.