At least 20% of human malignancies are caused by consequences of persistent infections. High-risk human papillomavirus (HPV) types cause over 500.000 cancer cases per year, rendering HPV the #2 human carcinogen after tobacco. Infection-related tumours are attractive targets for cancer vaccination, as they provide the opportunity to target antigens that are immunological non-self. Vaccination can be prophylactic, inducing immune responses preventing infection in the first place, or therapeutic, stimulating the immune system into eradicating established disease. Prophylactic immunization against HPV has become the paradigm for cancer immunoprevention. Unfortunately, current HPV vaccines have no therapeutic effect on existing infections. Studies on spontaneously regressing HPV-induced lesions show that cell-mediated immune responses are crucial in clearing established HPV infection. Cytotoxic T cells (CTL) kill infected cells after recognizing viral epitopes presented on HLA molecules on the cell surface. There are hundreds of different HLA types, and a given epitope is only applicable for the fraction of patients with the relevant HLA molecule.
This project will define a set of T cell epitopes that elicit CTL-mediated HPV protection in the entire population, by including epitopes for all HLA supertypes. The applicant has established a methodology of determining which viral epitopes are presented on target cells during her past mobility period in the US. HPV-transformed cells of various HLA backgrounds are analyzed by nanospray mass spectrometry. Identified peptides are tested for immunogenicity and the ability to induce CTL. From these tests, a minimal set of functional epitopes providing >95% population protection coverage is selected for vaccine formulation. The technology is currently transferred to the DKFZ. If this epitope-specific, yet widely applicable therapeutic vaccination approach is successful, it can be used as a platform technology in other malignancies.
Start Date: 2011-12-01 End Date: 2015-11-30 EU Contribution: 100 000 Euro Total Costs: 100 000 Euro Programme Acronym: FP7-People Subprogramme Area: FP7-PEOPLE-2011-CIG Marie-Curie Action: "Career Integration Grants"
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