T. Fukui et al., Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector, ORAL ONCOL, 37(3), 2001, pp. 211-215
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.