Coexpression of Flt3 ligand and GM-CSF genes modulates immune responses induced by HER2/neu DNA vaccine.
DNA vaccine and dendritic cells (DCs)-based vaccine have emerged as promising strategies for cancer immunotherapy. Fms-like tyrosine kinase 3-ligand (Flt3L) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) have been exploited for the expansion of DC. It was reported previously that combination of plasmid encoding GM-CSF with HER2/neu DNA vaccine induced predominantly CD4(+) T-cell-mediated antitumor immune response. In this study, we investigated the modulation of immune responses by murine Flt3L and GM-CSF, which acted as genetic adjuvants in the forms of bicistronic (pFLAG) and monocistronic (pFL and pGM) plasmids for HER2/neu DNA vaccine (pN-neu). Coexpression of Flt3L and GM-CSF significantly enhanced maturation and antigen-presentation abilities of splenic DC. Increased numbers of infiltrating DC at the immunization site, higher interferon-gamma production, and enhanced cytolytic activities by splenocytes were prominent in mice vaccinated with pN-neu in conjunction with pFLAG. Importantly, a potent CD8(+) T-cell-mediated antitumor immunity against bladder tumors naturally overexpressing HER2/neu was induced in the vaccinated mice. Collectively, our results indicate that murine Flt3L and GM-CSF genes coexpressed by a bicistronic plasmid modulate the class of immune responses and may be superior to those codelivered by two separate monocistronic plasmids as the genetic adjuvants for HER2/neu DNA vaccine.
Yo
Y-T
YT
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
Hsu
K-F
KF
Shieh
G-S
GS
Lo
C-W
CW
Chang
C-C
CC
Wu
C-L
CL
Shiau
A-L
AL
D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D010957:Plasmids / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000627:therapeutic use
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008565:Membrane Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C084881:flt3 ligand protein