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Dendritic cells expressing a combined PADRE/MUC4-derived polyepitope DNA vaccine induce multiple cytotoxic T-cell responses.
发布时间:2016-06-25   浏览次数:951

Abstract

The tumor-associated antigen, mucin4(MUC4), is overexpressed on various epithelial malignancies, making it apotentially broadly applicable candidate vaccine therapy. In this paper, wereport on the creation of a dendritic cell (DC)-based vaccine, using cellstransduced with the universal DR-restricted Th helper epitope (PADRE) combinedwith human leukocyte antigen (HLA)-A1- and HLA-A2-restricted epitopes from MUC4(rAd-pE-DCs). We examined this vaccine's biologic characteristics and immuneactivity in vitro, finding that infection with the polyepitope adenovirus didnot alter the typical morphology of mature DC and the typical markers of thesecells (CD86, CD83, CD80, and HLA-DR) were highly expressed on rAd-pE-DCs.Lymphocytes primed with rAd-pE-DCs generated potent cytotoxic responses. Bycontrast, lymphocytes primed with a GFP-expressing adenovirus (rAd-GFP-DCs) ormock-transfected DCs were not cytotoxic. Transduction of DCs with an adenovirusencoding PADRE combined with HLA-A1- and HLA-A2-restricted epitopes may be apotential strategy for the immunotherapy of MUC4-associated tumors.