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.

Riediger, Carina; Wingender, Gerhard; Knolle, Percy; Aulmann, Sebastian; Stremmel, Wolfgang; Encke, Jens

doi:10.1007/s00432-013-1532-z

2013

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Dokumenttyp:: Journal Article; Article
Autor(en):: Riediger, Carina; Wingender, Gerhard; Knolle, Percy; Aulmann, Sebastian; Stremmel, Wolfgang; Encke, Jens
Titel:: 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:: 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.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.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).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.
Zeitschriftentitel:: J Cancer Res Clin Oncol
Jahr:: 2013
Band / Volume:: 139
Heft / Issue:: 12
Seitenangaben Beitrag:: 2097-110
Sprache:: eng
Volltext / DOI:: doi:10.1007/s00432-013-1532-z
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/24114287
Print-ISSN:: 0171-5216
TUM Einrichtung:: Roman Herzog Comprehensive Cancer Center
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Roman Herzog Comprehensive Cancer Center 2013