The overall aim of this project is to determine the efficacy of papillomavirus-like particles (VLPs) as preventative and therapeutic vaccines fro human cervical cancer. The detailed experimental model described in the preliminary results involves the induction of tumors by injecting C3 cells (murine embryo cells transformed with full length HPV16 viral DNA together with activated ras) into syngeneic immunocompetent mice. The system has been validated by identifying an epitope of HPV16 E7 that induces an anti-tumor CTL response. A CTL clone recognizing this epitope prevents tumor formation in adoptive transfer experiments. This model will be used to test the effects of VLP immunization on the generation of anti-tumor immunity. These studies are relevant to the vaccination of human cervical carinomas that result from HPPV16 infection. The principal investigator also identified HPV16 E6 and E7 peptides recognized by human HLA-A allels that will facilitate the application of vaccine strategy to humans. In pursuit of this goal, the proposed investigations will to humans. In pursuit of this goal, the proposed investigations will also assess the ability of VLPs to induce an HLA restricted T cell response in HLA transgenic mice, as well as by in vitro immunization of human peripheral blood cells. p
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