HER-2/neu-gene engineered dendritic cell vaccine stimulates stronger HER-2/neu-specific immune responses compared to DNA vaccination.
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.
Chan
T
T
Cancer Research Unit, Saskatchewan Cancer Agency, University of Saskatchewan, 20 Campus Drive, Saskatoon, Saskatchewan, Canada S7N 4H4.
Sami
A
A
El-Gayed
A
A
Guo
X
X
Xiang
J
J
D000256:Adenoviridae / Q000235:genetics; D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D005786:Gene Expression Regulation; D018734:Genes, erbB-2; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007167:Immunotherapy / Q000379:methods; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage
D019496:Cancer Vaccines; D016207:Cytokines; D019444:Vaccines, DNA