A genetically retargeted adenoviral vector enhances viral transduction in esophageal carcinoma cell lines and primary cultured esophageal resection specimens.
OBJECTIVE
To evaluate if an integrin-retargeted adenoviral vector could establish a more efficient and tumor-specific gene transfer in esophageal carcinoma cells.


BACKGROUND
Although preclinical data indicated that adenoviral gene therapy could be a promising novel treatment modality for various malignancies, clinical results are often disappointing. An important problem is the decreased tumoral expression of the Coxsackie and adenovirus receptor (CAR), which mediates adenoviral entry. Retargeting the adenoviral vector to other cellular receptors, by inserting an arginine-glycine-aspartate (RGD) tripeptide in the fiber knob, might overcome this problem.


METHODS
Four esophageal carcinoma cell lines and 10 fresh surgical resection specimens were cultured. All were infected with the native adenovirus (Ad) and the retargeted adenovirus (AdRGD), encoding for the reporter genes luciferase or Green Fluorescent Protein to analyze gene transfer efficiency.


RESULTS
In all cell lines, an increase in viral expression per cell and an increase in the percentage of transduced cells were seen with the retargeted adenovirus. Also, in the primary cultures of carcinoma cells, a more efficient gene transfer was seen when the retargeted vector was used. This phenomenon was less pronounced in normal cells, indicating that the RGD virus transduces tumor cells more efficiently than normal cells.


CONCLUSIONS
This study demonstrates that an RGD retargeted adenovirus infects human esophageal carcinoma cells with enhanced efficiency, while in normal esophageal cells this effect is less pronounced. Therefore, this retargeted vector is expected to have a better performance in vivo, when compared with nonretargeted vectors used for cancer gene therapy so far.
Buskens
Christianne J
CJ
Academic Medical Center, Deptartment of Surgery, Suite G4-130, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. C.J.Buskens@AMC.UVA.NL
Marsman
Willem A
WA
Wesseling
John G
JG
Offerhaus
G Johan A
GJ
Yamamoto
Masato
M
Curiel
David T
DT
Bosma
Piter J
PJ
van Lanschot
J Jan B
JJ
D000230:Adenocarcinoma / Q000628:therapy*; D000256:Adenoviridae; D045744:Cell Line, Tumor; D046508:Culture Techniques; D004938:Esophageal Neoplasms / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans