title: Vaccination against the HER-2/neu oncogenic protein.
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.
authors.affiliation: Technical University of Munich, Klinikum rechts der Isar, Department of Hematology and Oncology, Ismaningerstrasse 22, D-81664 Munich, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bernhard
authors.forename: L
authors.initials: L
authors.lastname: Salazar
authors.forename: K
authors.initials: K
authors.lastname: Schiffman
authors.forename: A
authors.initials: A
authors.lastname: Smorlesi
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.forename: K L
authors.initials: KL
authors.lastname: Knutson
authors.forename: M L
authors.initials: ML
authors.lastname: Disis
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology / Q000592:standards
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; D022223:Vaccines, Subunit