Vaccination of fiber-modified adenovirus-transfected dendritic cells to express HER-2/neu stimulates efficient HER-2/neu-specific humoral and CTL responses and reduces breast carcinogenesis in transgenic mice.
HER-2/neu transgene-modified dendritic cell (DC)-based vaccines are potent at eliciting HER-2/neu-specific antitumor immunity. In this study, we constructed a recombinant adenovirus (RGD)AdVneu with fiber gene modified by RGD insertion into the viral knob's H1 loop. We transfected DCs with (RGD)AdVneu, and assessed/compared HER-2/neu-specific humoral and cytotoxic T lymphocyte (CTL) responses and antitumor immunity derived from the original AdVneu-transfected DCs (DCneu1) and (RGD)AdVneu-transfected DCs (DCneu2). We demonstrated that DCneu2 displayed increased HER-2/neu expression by 8.3-fold compared to DCneu1. We also demonstrated that DCneu2 vaccination induced stronger HER-2/neu-specific humoral and CTL immune responses than DCneu1 vaccination. DCneu2 vaccination protected all the mice from HER-2/neu-expressing Tg1-1 tumor cell challenge in wild-type FVB/NJ mice, compared to a partial protection in DCneu1-immunized mice. In addition, DCneu2 vaccination also significantly delayed tumor growth than DCneu1 immunization (P<0.05) in Tg FVBneuN mice. Three immunizations of DCneu2 starting at the mouse age of 2 months also significantly delayed breast cancer development in Tg mice compared to DCneu2 vaccine (P<0.05). Importantly, DCneu2 vaccine reduced breast carcinogenesis by 9% in Tg mice with self HER-2/neu tolerance. Therefore, vaccination of fiber-modified adenovirus-transfected DCs to enhance expression of tumor antigens such as HER-2/neu is likely representative of a new direction in DC-based vaccine of breast cancer.
Sas
S
S
Division of Oncology, Cancer Research Unit, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Chan
T
T
Sami
A
A
El-Gayed
A
A
Xiang
J
J
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018734:Genes, erbB-2 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019496:Cancer Vaccines