title: Fms-like tyrosine kinase 3 receptor ligand (Flt3L)-based vaccination administered with an adenoviral vector prevents tumor growth of colorectal cancer in a BALB/c mouse model.
abstract: OBJECTIVE
  Colorectal cancer is the third most frequent cancer in industrial nations. Therapeutic strategies to treat metastatic disease and prevent recurrence are needed. Anti-tumor immunity can be induced by dendritic cells. Dendritic cells can be expanded by the fms-like tyrosine kinase 3 ligand (Flt3L) in vivo. The aim of this study was to develop an adenoviral-based immune-gene therapy of colorectal cancer with Flt3L in a BALB/c mouse model.
  
  
  METHODS
  A new Flt3L-encoding adenoviral vector (pAdFlt3L) was administered in two approaches in a CT26 colon cancer model in female BALB/c mice. In the therapeutic approach, pAdFlt3L was injected into the tail vein or directly into subcutaneous CT26 colon carcinoma tumors in BALB/c mice. In the vaccination protocol, mice were vaccinated with CT26 cell lysate and pAdFlt3L subcutaneous prior to subcutaneous application of vital CT26 cells.
  
  
  RESULTS
  Application of pAdFlt3L led to high levels of Flt3L in vitro and in vivo. Significant expansion of dendritic cells after application of pAdFlt3L in vivo was confirmed by the use of CD11c and CD11b surface markers in immunohistochemistry and flow cytometry (p = 0.019). In the therapeutic approach, neither intravenous nor intratumoral treatments with pAdFlt3L lead to regression of CT26 tumors. In the vaccination protocol, vaccination completely prevented tumor growth and resulted in superior survival compared to control mice (p < 0.001).
  
  
  CONCLUSIONS
  Our results demonstrate that immunostimulatory therapy with pAdFlt3L is effective to prevent tumor development through vaccination and may represent a therapeutic tool to prevent metastatic disease.
authors.affiliation: Department of Internal Medicine IV and Otto-Meyerhof-Center for Medical Sciences, University of Heidelberg, Heidelberg, Germany, Carina.Riediger@uniklinikum-dresden.de.
authors.forename: Carina
authors.initials: C
authors.lastname: Riediger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wingender
authors.forename: Percy
authors.initials: P
authors.lastname: Knolle
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aulmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.forename: Jens
authors.initials: J
authors.lastname: Encke
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D007167:Immunotherapy; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured; D014611:Vaccination; D023041:Xenograft Model Antitumor Assays
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein