Si. Miyatake et al., DEFECTIVE HERPES-SIMPLEX VIRUS VECTORS EXPRESSING THYMIDINE KINASE FOR THE TREATMENT OF MALIGNANT GLIOMA, Cancer gene therapy, 4(4), 1997, pp. 222-228
Viral vectors used for cancer gene therapy have usually been either re
plication-incompetent vectors expressing a gene product that leads to
the destruction of the tumor or replication-competent vectors that are
inherently cytotoxic to the tumor cells. We have sought to combine th
e attributes of these different approaches using a defective herpes si
mplex virus (HSV) vector that consists of a defective particle, contai
ning tandem repeats of the HSV thymidine kinase (TK) gene, and a repli
cation-competent, non-neurovirulent HSV mutant as a helper virus. HSV-
TK activity in defective vector-infected cells was significantly great
er than that in helper virus-infected cells which contained a single c
opy of HSV-TK. infection of cells with this defective vector renders t
hem, as well as surrounding uninfected cells, sensitive to killing by
ganciclovir. Ganciclovir treatment of C57BL/6 mice bearing TK-defectiv
e vector/helper virus-infected subcutaneous GL261 gliomas resulted in
significantly decreased tumor size.