Immunization to oncogenic HER-2/neu protein with peptide based vaccines (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Immunization to oncogenic HER-2/neu protein with peptide based vaccines (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A1498 1995. Unique Identifier : AIDSLINE ICDB/95609275
Disis ML; Gralow JR; Bernhard H; Hand S; Cheever MA; Medical Oncology, Univ. of Washington, RM-17, Seattle, WA 98195

Abstract: Studies from our laboratory have shown that HER-2/neu (c-erbB-2) protein is a tumor antigen. Some patients with breast cancer have existent antibody and CD4+ T cell responses against the protein. The detection of existent immunity to HER-2/neu was surprising, since HER-2/neu is a 'self' protein and immunological tolerance to self was expected. The goal of the current studies was to identify HER-2/neu based vaccine formulations capable of prospectively circumventing tolerance and eliciting immunity. The long-term goal is to identify therapeutic vaccines appropriate for testing in humans. Methods to generate immune responses to 'self' tumor antigens are not well established. The ploy used to circumvent tolerance to whole protein was to test immunization to synthetic subunit peptides with amino acid motifs appropriate for binding to class II MHC molecules. Human and rat neu are highly homologous (89%) and peptides used were 100% homologous between the two species. Animals were immunized with groups of peptides derived from the amino acid sequence of the intra (ICD) or extra (ECD) cellular domains of neu protein. Rats in both groups developed substantial CD4+ T cell and IgG antibody responses to rat neu. The CD4+ T cell proliferative responses were specific for both ICD and ECD peptides. Mapping of the antibody responses revealed predominant B cell epitopes in both domains of the protein. Importantly, the antibodies elicited were reactive to and capable of immunoprecipitating both human and rat neu. These studies point to both an immunization strategy and to peptide epitopes that might be effective in human breast cancer vaccines.

Keywords: Animal Breast Neoplasms/IMMUNOLOGY/THERAPY CD4 Lymphocyte Count CD4-Positive T-Lymphocytes/IMMUNOLOGY Female Human Immunotherapy, Active Proto-Oncogene Proteins c-erbB-2/*IMMUNOLOGY Rats Vaccines, Synthetic/*IMMUNOLOGY ABSTRACT
950930
M9591324

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