Efficacy of transfection rates on head and neck squamous cell cancer by a novel adenovirus: an in vivo and in vitro study.
BACKGROUND
Internalization of wild-type adenovirus is dependent on binding to a coxsackie-adenovirus receptor (CAR). Unfortunately, many tumors lack these receptors. We hypothesized that a novel RGD adenovirus, which binds by way of cellular integrins, would improve the transfection of head and neck cancers.


METHODS
Three squamous cell cancer lines were transfected with either the wild type or the novel RGD containing a luciferase reporter gene. After 48 hours, the transfection rate was determined. This was correlated with CAR and alphaVbeta3 and alphaVbeta5 integrin expression as determined by flow cytometry. A similar experiment was performed in a nude mouse model to determine in vivo differences of transfection rate.


RESULTS
Statistically significant increased rates of transfection were seen for the novel adenovirus at all multiplicities of infection (MOIs) in the CAL-27 and SCC-4 cell lines. Increased rates of transfection were seen at lower viral titers for the SCC-25 cells. Flow cytometry revealed low CAR expression in all cell lines but no consistent pattern of integrin expression. The nude mouse model demonstrated a 43-fold higher rate of transfection for the novel RGD adenovirus.


CONCLUSIONS
A modified RGD adenovirus increased the efficacy of transfection in specific cell lines and in the nude mouse model. It is possible that modified adenoviruses may improve gene delivery to patients with advanced or recurrent head and neck cancers.
Lalonde
Elise S
ES
Department of Otolaryngology and Biocommunication, Louisiana State University Health Sciences Center, 533 Bolivar Street, 5th Floor, Louisiana 70112, USA. pfried@lsumc.edu
Beyer
Gregory
G
Friedlander
Paul L
PL
Kolls
Jay K
JK
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000258:Adenovirus Infections, Human / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D016023:Integrins / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D016023:Integrins; D011991:Receptors, Virus; D008156:Luciferases