Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector

The purpose of this study was to test the possibility of gene transfer as a new therapy for oral cancer. Adeno-associated virus (AAV) has already been used in the fields of cystic fibrosis and Parkinson's disease as a potenti al vector for gene therapy because of its wide host range, high transductio n efficiency, and lack of cytopathogenicity. Four human oral squamous cell carcinoma cell lines were transduced with an AAV vector containing the P-ga lactosidase gene (AAVlacZ) in vitro. Gene transduction efficiency was from 20 to 50% at a multiplicity of infection (MOI; for the purposes of this stu dy the number of vector genomes per target cell) of 1 x 10(3), and nearly 1 00% of each cell line were transduced at an MOI of 1 x 10(4). Next, four ce ll lines were transduced with an AAV vector containing the herpes simplex v irus thymidine kinase (HSVtk) gene, which sensitizes transduced cells to ga nciclovir (GCV). Subsequent administration of GCV resulted in nearly 100% t umor cell killing at an MOI of 1 x 10(4) and from 70 to 80% tumor cell kill ing at an MOI of 1 x 10(3). These results suggest that AAV-mediated gene tr ansfer of HSVtk and administration of GCV has potential as a new therapy fo r oral squamous cell carcinoma. (C) 2001 Elsevier Science Ltd. All rights r eserved.