Vaccination against the HER-2/neu oncogenic protein.
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.
Bernhard
H
H
Technical University of Munich, Klinikum rechts der Isar, Department of Hematology and Oncology, Ismaningerstrasse 22, D-81664 Munich, Germany.
Salazar
L
L
Schiffman
K
K
Smorlesi
A
A
Schmidt
B
B
Knutson
K L
KL
Disis
M L
ML
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
D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; D022223:Vaccines, Subunit