The HER-2/neu oncogene is amplified and overexpressed in 20-40% of intraductal carcinomas of the breast and 30% of ovarian cancers. Overexpression of the protein in both these malignancies is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. Preliminary studies have shown that some patients with breast cancer have existent T cell and antibody immunity to HER-2/neu. HER-2/neu is a self protein. Therefore, it had been assumed that patients would be immunologically tolerant and that immunity could not be generated. Immunization studies performed in rats, the only other species where neu has been sequenced, demonstrated that rats are tolerant to rat neu protein. Immunity could not be generated with protein immunization. Rat neu specific immunity could be elicited in rats, however, by vaccination with immunogenic peptides. HER-2/neu peptide based vaccines may be the most effective way to augment HER-2/neu specific immunity in patients with no detectable neu directed immune response. The applicant's studies demonstrating that immunity is already present in some patients with breast cancer imply that immunity to HER-2/neu is induced in some individuals by virtue of the presence of growing cancer expressing the antigen and gives credence to the concept that HER-2/neu specific immunity can be used in therapy without destroying normal tissue. This application outlines a Phase I study of H2N peptide based vaccine, with GM-CSF as an adjuvant, in patients with advanced stage H2N expressing cancers. The investigation has been approved for human study by both the United States Food and Drug Administration (FDA IND BB-6524, Disis P.I.) and the University of Washington
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| Disis, Mary L; Goodell, Vivian; Schiffman, Kathy et al. (2004) Humoral epitope-spreading following immunization with a HER-2/neu peptide based vaccine in cancer patients. J Clin Immunol 24:571-8 |
| Disis, Mary L; Salazar, Lupe G; Knutson, Keith L (2004) Peptide-based vaccines in breast cancer. Breast Dis 20:3-11 |
| McNeel, Douglas G; Knutson, Keith L; Schiffman, Kathy et al. (2003) Pilot study of an HLA-A2 peptide vaccine using flt3 ligand as a systemic vaccine adjuvant. J Clin Immunol 23:62-72 |
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| Disis, Mary L; Schiffman, Kathy; Salazar, Lupe G et al. (2003) HER-2/neu vaccines. Cancer Chemother Biol Response Modif 21:275-85 |
| Disis, Mary L; Gooley, Theodore A; Rinn, Kristine et al. (2002) Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol 20:2624-32 |
| Knutson, Keith L; Schiffman, Kathy; Cheever, Martin A et al. (2002) Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity. Clin Cancer Res 8:1014-8 |
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