BACKGROUND: DNA 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. METHODS: In 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. RESULTS: The 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-gamma secretion. CONCLUSIONS: The 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 (c) 2010 John Wiley & Sons, Ltd.
BACKGROUND: DNA 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 humantumors, 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. METHODS: In 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. RESULTS: The 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-gamma secretion. CONCLUSIONS: The 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 (c) 2010 John Wiley & Sons, Ltd.