The aim of this proposal is the generation of a murine model of Human Papilloma Virus associated cancer that will allow us to specifically test the efficacy of a new class of heat shock protein based vaccines using HLA-A2 restricted HPV-16 E7 epitopes. HPV associated malignancies are the second most common cause of cancer death in women worldwide. Such malignancies are an ideal target for immunotherapy due to the uniform expression of E6 and E7. Furthermore, the capacity of the human immune system to recognize the E7 antigen has been well documented based on the detection of both antibody responses as well as CTL responses. Specifically, they propose to: Introduce a chimeric HLA-A2.1/Kb and a human beta2 microglobulin gene into the established E6/E7+ murine TC-1 tumor (TC-1/A2). Validate that TC-1/A2 can indeed be recognized by HLA-A2 restricted T cells. Produce HSP70 vaccines using a proprietary peptide technology. Assessing the growth kinetics and immunogenicity of TC-1/A2 in HLA-A2/Kb transgenic mice determines whether immunization with the HSP70:HPV16E7-70BP peptide vaccines delay outgrowth of TC-1/A2 tumors. If the HSP70 vaccines demonstrate antitumor efficacy in this model for HPV associated malignancy, they will be developed for clinical trials.
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