Dendritic cells expressing a combined PADRE/MUC4-derived polyepitope DNA vaccine induce multiple cytotoxic T-cell responses.
The tumor-associated antigen, mucin4 (MUC4), is overexpressed on various epithelial malignancies, making it a potentially broadly applicable candidate vaccine therapy. In this paper, we report on the creation of a dendritic cell (DC)-based vaccine, using cells transduced with the universal DR-restricted Th helper epitope (PADRE) combined with human leukocyte antigen (HLA)-A1- and HLA-A2-restricted epitopes from MUC4 (rAd-pE-DCs). We examined this vaccine's biologic characteristics and immune activity in vitro, finding that infection with the polyepitope adenovirus did not alter the typical morphology of mature DC and the typical markers of these cells (CD86, CD83, CD80, and HLA-DR) were highly expressed on rAd-pE-DCs. Lymphocytes primed with rAd-pE-DCs generated potent cytotoxic responses. By contrast, lymphocytes primed with a GFP-expressing adenovirus (rAd-GFP-DCs) or mock-transfected DCs were not cytotoxic. Transduction of DCs with an adenovirus encoding PADRE combined with HLA-A1- and HLA-A2-restricted epitopes may be a potential strategy for the immunotherapy of MUC4-associated tumors.
Wei
Jishu
J
Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Gao
Wentao
W
Wu
Junli
J
Meng
Kai
K
Zhang
Jingjing
J
Chen
Jianmin
J
Miao
Yi
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005818:Genetic Engineering; D006801:Humans; D007371:Interferon-gamma; D017780:Malaria Vaccines / Q000276:immunology*; D008969:Molecular Sequence Data; D055264:Mucin-4; D009077:Mucins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000939:Epitopes; C524658:MUC4 protein, human; D017780:Malaria Vaccines; D055264:Mucin-4; D009077:Mucins; C401223:PADRE 45; D019444:Vaccines, DNA; D007371:Interferon-gamma