GP96 C‐terminal improves Her2/neu DNA vaccine

AbstractBackgroundDNA vaccines ensure protective immunity against tumors in a variety of experimental models. The favorite target tumor‐associated antigens have been those that are frequently expressed by human tumors, such as Her2. However, the efficacy of active vaccination is limited because Her2 is a self‐tolerated antigen. Many strategies have been applied to increase the efficacy of DNA vaccination, such as fusion or co‐administration of Her2 with cytokine and co‐stimulatory molecules. GP96 is involved in innate and adaptive immune responses and evokes potent activation and maturation of dendritic cells along with increased secretion of pro‐inflammatory cytokines. On the basis of previous studies, we expected the C‐terminal of GP96 to act as a package and as a suitable substitute for both cytokine and co‐stimulatory genes.MethodsIn the present study, the C‐terminal of GP96 fused or co‐administered with Her2/neu‐containing constructs was used and the resultant immune response was evaluated and compared.ResultsThe data obtained showed that the construct containing the C‐terminal of GP96 fused with Her2/neu, but not the co‐administration of the two separated constructs, decreased CD4+CD25+foxp3+ regulatory T cells at the tumor site, enhanced cytotoxic T lymphocyte activity and increased interferon‐γ secretion.ConclusionsThe C‐terminal of GP96 has potent adjuvant activity in eliciting a significant immune response when fused with Her2/neu. It may be used as molecular adjuvant along with other tumor or bacterial/viral antigens. Copyright © 2010 John Wiley & Sons, Ltd.