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Duane A. Sewell, MD; Daqing Li, MD; Ling Duan, MS; William H. Westra, MD; Bert W. O'Malley, Jr, MD

Arch Otolaryngol Head Neck Surg. 1997;123(12):1298-1302.

Abstract
Background
Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene (tk) is one of the most effective gene therapy strategies for solid tumors in experimental animal studies. Foundational animal studies in an oral cancer model have demonstrated significant antitumor effects and improved animal survival using this treatment strategy.

Objective
To assess the safety of adenovirusmediated transfer of the herpes simplex virus tk gene for the treatment of oral cancer.

Design
Oral tumors were established in C3H/HeJ mice and were treated with tk followed by systemic ganciclovir administration. Polymerase chain reaction amplification techniques were used to screen local surrounding tissues and distant organs for the presence of the adenoviral construct. Microscopic examination of the tissues was performed to determine the cytopathic effects of the vector. Blood samples were obtained from the animals to test for liver, renal, and bone marrow function after treatment.

Results
The adenoviral vector was present in the livers, lungs, and kidneys of animals treated with the maximal single injection dose of 2x10⁹ plaque forming units (pfu). No vector was noted systemically after delivery of an equally effective low dose of 1x10⁸ pfu. Microscopic examination revealed no cytopathic effects in distant organs despite the presence of vector. Results of liver and renal function tests revealed no differences between treated and control animals. There was no statistical difference in white blood cell count, hematocrit, or platelet count between animals treated with ganciclovir and control animals.

Conclusions
Based on these results, the direct delivery of adenovirus-tk followed by ganciclovir administration appears both efficacious and safe in an animal model. However, serum evaluation for adenovirus vector and screening organ function studies should be included in human protocols using this gene therapy scheme.

Arch Otolaryngol Head Neck Surg. 1997;123:1298-1302

Author Affiliations
From the Departments of Otolaryngology—Head and Neck Surgery (Drs Sewell, Li, and O'Malley and Ms Duan) and Pathology (Dr Westra), Johns Hopkins Medical Institutions, Baltimore, Md.

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