Vaccine strategies are being investigated as another method of targeting HER2 overex-pressing cancer cells. Patients with HER2-positive tumors have been shown to develop an immune response against the protein,114-116 which suggests that antireceptor vaccines may be successful in mounting an anticancer response. With a large difference in levels of expression between HER2-positive tumors and normal tissues, there exists a potential therapeutic window for such cancers with no residual autoimmune toxicity. Some of the first described investigations of targeting and treating by immunization were murine tumors overexpressing the rat oncogenic neu. These cancers were immunized with a vaccinia virus recombinant of the protein's extracellular domain.117 Both intracellular and extracellular portions of the HER2 receptor have been shown to elicit specific responses from cyto-toxic T-lymphocytes (CTL). Immunizing rats with peptides derived from the self-rat Neu, but not with the whole protein, is known to promote antibody and T-cell responses against the native protein.118 Nagata et al119 have subsequently shown that similar peptides, derived from the murine ErbB-2 receptor, can induce CTL activity, which results in the suppression of growth of HER2 overexpressed cells in syn-geneic hosts.
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