Vaccination against the HER-2/neu oncogenic protein

H. Bernhard, L. Salazar, K. Schiffman, A. Smorlesi, B. Schmidt, K. L. Knutson, M. L. Disis

Research output: Contribution to journalReview article

50 Scopus citations

Abstract

The HER-2/neu oncogenic protein is a well-defined tumor antigen. HER-2/neu is a shared antigen among multiple tumor types. Patients with HER-2/neu protein-overexpressing breast, ovarian, non-small cell lung, colon, and prostate cancers have been shown to have a pre-existent immune response to HER-2/neu. No matter what the tumor type, endogenous immunity to HER-2/neu detected in cancer patients demonstrates two predominant characteristics. First, HER-2/neu-specific immune responses are found in only a minority of patients whose tumors overexpress HER-2/neu. Secondly, immunity, if detectable, is of low magnitude. These observations have led to the development of vaccine strategies designed to boost HER-2/neu immunity in a majority of patients. HER-2/ neu is a non-mutated self-protein, therefore vaccines must be developed based on immunologic principles focused on circumventing tolerance, a primary mechanism of tumor immune escape. HER-2/neu-specific vaccines have been tested in human clinical trials. Early results demonstrate that significant levels of HER-2/neu immunity can be generated with active immunization. The T-cell immunity elicited is durable after vaccinations have ended. Furthermore, despite the generation of CD8+ and CD4+ T-cells responsive to HER-2/neu in a majority of patients, there is no evidence of autoimmunity directed against tissues that express basal levels of the protein. Cancer vaccines targeting the HER-2/neu oncogenic protein may be useful adjuvants to standard therapy and aid in the prevention of relapse in patients whose tumors overexpress the protein. Furthermore, boosting HER-2/neu-specific T-cell frequencies via active immunization may allow the ex vivo expansion of HER-2/neu-specific T-cells for use in adoptive immunotherapy, a therapeutic strategy directed against the treatment of established disease.

Original languageEnglish (US)
Pages (from-to)33-44
Number of pages12
JournalEndocrine-Related Cancer
Volume9
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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    Bernhard, H., Salazar, L., Schiffman, K., Smorlesi, A., Schmidt, B., Knutson, K. L., & Disis, M. L. (2002). Vaccination against the HER-2/neu oncogenic protein. Endocrine-Related Cancer, 9(1), 33-44. https://doi.org/10.1677/erc.0.0090033