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Immunotherapy in new pre-clinical models of HPV-associated oral cancers

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Immunotherapy in new pre-clinical models of HPV-associated oral cancers

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Paolini, Francesca Massa, Silvia Manni, Isabella Franconi, Rosella Venuti, Aldo
Description	Country affiliation: Italy Author Affiliation: Paolini F ( Laboratory of Virology)
Abstract	Cervical, anal, penile and a sub-set of head and neck (HN) tumors are critical health problems caused by high risk Human Papilloma Viruses (HPVs), like HPV type 16. No specific/effective pharmacological treatments exist. A valid preventive vaccination as well as the immunotherapy of persistent infections, pre-cancerous lesions or early-stage cancers could drive the HPV disease burden down. These treatments might be featured through low-cost platforms like those based on DNA and plant biotechnologies to produce tailored and enhanced formulations taking profit from the use of plants as bio-factories and as a source of immune-stimulators. Finally, and regardless of the formulation type, pre-clinical tests and models are crucial to foresee efficacy of immunotherapy before clinical trials. In this study, we created an orthotopic mouse model for HPV-related oral tumors, a subset of HN tumors for which no models have been generated before. The model was obtained by inducing the stable expression of the HPV16 E7 protein into the mouse oral squamous cell carcinoma (OSCC) AT-84 (AT-84 E7). The AT-84 E7 cells were injected into the mouth pavement of C3H mice via an extra-oral route to obtain orthotopic tumors. The model turned out to mimic the natural history of the human HPV oral cancer. From AT-84 E7, through engineering to express luciferase, the bioluminescent AT-84 E7-Luc cells were obtained for a fast and easy monitoring by imaging. The AT-84 E7 and the AT-84 E7-Luc tumors were used to test the efficacy of E7-based therapeutic vaccines that we had previously generated and that had been already proven to be active in mice against non-orthotopic E7-expressing tumors (TC-1 cells). In particular, we used genetic and plant-derived formulations based on attenuated HPV16 E7 variants either fused to plant virus genes with immunological activity or produced by tobacco plants. Mice were monitored by imaging allowing to test the size reduction of the mouth implanted experimental tumors in function of the different regimens used. The proposed tumor model is easy to handle and to reproduce and it is efficacious in monitoring immunotherapy. Furthermore, it is expected to be more predictive of clinical outcome of therapeutic vaccines than non-orthotopic models that are currently used. Finally, imaging offers unique opportunities to predict formulation efficacy through measuring tumor growth in vivo.
File Format	HTM / HTML
ISSN	21645515
e-ISSN	2164554X
Journal	Human Vaccines & Immunotherapeutics
Issue Number	3
Volume Number	9
Language	English
Publisher	Taylor & Francis
Publisher Date	2013-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Immunology Discipline Therapeutics Disease Models, Animal Immunotherapy Mouth Neoplasms Therapy Papillomavirus Infections Complications Animals Cancer Vaccines Administration & Dosage Immunology Cell Line, Tumor Genes, Reporter Luciferases Genetics Mice, Inbred C3h Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Pharmacology

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