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Publication : HER-2/neu-gene engineered dendritic cell vaccine stimulates stronger HER-2/neu-specific immune responses compared to DNA vaccination.

First Author  Chan T Year  2006
Journal  Gene Ther Volume  13
Issue  19 Pages  1391-402
PubMed ID  16724093 Mgi Jnum  J:115815
Mgi Id  MGI:3692230 Doi  10.1038/sj.gt.3302797
Citation  Chan T, et al. (2006) HER-2/neu-gene engineered dendritic cell vaccine stimulates stronger HER-2/neu-specific immune responses compared to DNA vaccination. Gene Ther 13(19):1391-402
abstractText  HER-2/neu is a candidate for developing breast cancer-targeted immunotherapeutics. Although DNA-based and HER-2/neu transgene-modified dendritic cell (DC)-based vaccines are potent at eliciting HER-2/neu-specific antitumor immunity, there has been no side-by-side study comparing them directly. The present study utilizes an in vivo murine tumor model expressing HER-2/neu antigen to compare the efficacy between adenovirus (AdVneu)-transfected dendritic cells (DC(neu)) and plasmid DNA (pcDNAneu) vaccine. Our data showed that DC(neu) upregulated the expression of immunologically important molecules and inflammatory cytokines and partially converted regulatory T (Tr)-cell suppression through interleukin-6 (IL-6) secretion. Vaccination of DC(neu) induced stronger HER-2/neu-specific humoral and cellular immune responses than DNA vaccination, which downregulated HER-2/neu expression and lysed HER-2/neu-positive tumor cells in vitro, respectively. In two HER-2/neu-expressing tumor models, DC(neu) completely protected mice from tumor cell challenge compared to partial or no protection observed in DNA-immunized mice. In addition, DC(neu) significantly delayed breast cancer development in transgenic mice in comparison to DNA vaccine (P<0.05). Taken together, we have demonstrated that HER-2/neu-gene-modified DC vaccine is more potent than DNA vaccine in both protective and preventive animal tumor models. Therefore, DCs genetically engineered to express tumor antigens such as HER-2/neu represent a new direction in DC vaccine of breast cancer.
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