Efficacy of transfection rates on head and neck squamous cell cancer by a novel adenovirus: An in vivo and in vitro study

Introduction 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 ne...

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Bibliographic Details
Published in:Head & neck 2002-12, Vol.24 (12), p.1038-1046
Main Authors: Lalonde, Elise S., Beyer, Gregory, Friedlander, Paul L., Kolls, Jay K.
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - metabolism
adenovirus
Adenovirus Infections, Human - genetics
Adenovirus Infections, Human - metabolism
Animals
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - virology
Flow Cytometry
gene therapy
Genetic Therapy - methods
Genetic Vectors
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - virology
integrin
Integrins - metabolism
Luciferases - metabolism
Mice
Mice, Nude
Receptors, Virus - biosynthesis
Receptors, Virus - genetics
squamous cell carcinoma
Transfection
Tumor Cells, Cultured
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Summary:Introduction 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. Materials and 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 αVβ3 and αVβ5 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. © 2002 Wiley Periodicals, Inc.
ISSN:1043-3074
1097-0347
DOI:10.1002/hed.10148