Adenoviral serotypes in gene therapy for esophageal carcinoma.
OBJECTIVE
Adenoviral gene therapy could potentially play a role in the treatment of esophageal cancer and Barrett's esophagus. The adenoviruses can be categorized in different serotypes. The goal of the present study was to investigate the transduction efficacy of different adenoviral serotypes in different models of esophageal cancer and Barrett's esophagus.


METHODS
Chimeras of the adenoviral serotype 5 backbone and fibers of serotypes 5, 16, 35, 40, and 50 were constructed with PCR technology. For esophageal cancer, cell lines were used originating from with adenocarcinoma and squamous cell carcinoma, respectively. Differentiating Caco-2 cells were used as an in vitro model for Barrett's esophagus. GFP was used as a reporter gene and transduction efficacy was assessed by flow cytometry.


RESULTS
Overall transduction was rather efficient in the cancer cell lines. Especially serotype 16 and 50 exhibited an improved transduction compared with the other serotypes. In the Caco-2 cell lines, we observed a decreased transduction upon differentiation of the cells. All serotypes had a very limited transduction and no serotype had an additional value in this setting.


CONCLUSIONS
Some serotypes could have an additional value in the development of gene therapy for esophageal cancer. Especially serotype 16 and 50 exhibited an improved transduction in esophageal cancer cells compared with the native serotype 5. In the setting of Barrett's esophagus, none of the serotypes had an improved potency as in differentiated intestinal cells all serotypes had a very limited transduction.
Marsman
Willem A
WA
Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands. w.a.marsman@amc.uva.nl
Wesseling
John G
JG
El Bouch
Abelkarim
A
Bosma
Piter J
PJ
van Lanschot
J Jan B
JJ
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy; D000256:Adenoviridae / Q000145:classification* / Q000235:genetics*; D001471:Barrett Esophagus / Q000473:pathology / Q000628:therapy; D018938:Caco-2 Cells; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D012703:Serotyping; D014161:Transduction, Genetic / Q000379:methods