Research Project
6736431
DESCRIPTION (provided by applicant): Cervical cancer, the second most common cancer in women worldwide, is caused by chronic human papilloma virus (HPV) infection. Since precancerous squamous intraepithelial lesions (SIL) and cervical cancer continuously express HPV antigens, this cancer is theoretically curable by therapeutic vaccination. Preclinical studies and preliminary clinical studies have indicated feasibility of therapeutic vaccination of women with SIL. Eradication of the lesions is based on cell-mediated immune response. Immunization strategies capable of inducing cellular immunity against a broad array of HPV epitopes are actively sought. Plasmid DNA (pDNA) vaccination represents an appealing strategy because of its ability to elicit T cell responses, and because several antigens can be included in a single vaccine. Also, plasmid DNA is economical, easy to produce, store and standardize, and should induce few, if any, side effects. For pDNA vaccines, the method of administration is critical for efficacy. Vaccine will be delivered by electroporation because this method provides consistent, high-level, scalable immunogen expression, which correlates with vigorous, high-magnitude immune responses. Mice will be immunized with a previously characterized polyepitope DNA vaccine against HPV. End points will include induction of T cell responses, protection against lethal challenge by HPV-induced tumor cells, and eradication of established HPV-induced tumors.
