Improvement of gene therapy for ovarian cancer by using acyclovir instead of ganciclovir in adenovirus mediated thymidine kinase gene therapy.
Adenovirus(ADV) mediated thymidine kinase(TK) gene therapy followed by ganciclovir(GCV) administration is widely used in different types of cancer. ACV shares the same mechanism of selective cell killing in ADV/TK positive cells as GCV and can be used at 4.5 times higher doses in patients without significant side effects. An increased dose of TK substrate is associated with improved bystander effect and more efficient cell killing. Toxicity and cell killing efficacy were assessed using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide(MTT) based assay in three ovarian cancer cell lines with different proliferation patterns. At the same concentration, equal or higher cell killing efficacy and bystander effect were observed using ACV rather than GCV. 2.5 and 5 times (25 micrograms/ml and 50 micrograms/ml) higher concentrations of ACV always resulted in more effective cell killing than GCV (10 micrograms/ml, P < 0.01). Our data indicate that replacing GCV with ACV in the ADV-TK gene therapy may increase the treatment effect without increasing toxicity.
Tong
X W
XW
Department of Obstetrics and Gynecology, Baylor College of Medicine Houston, TX 77030, USA.
Engehausen
D G
DG
Kaufman
R H
RH
Agoulnik
I
I
Contant
C
C
Freund
C T
CT
Oehler
M K
MK
Kim
T E
TE
Hasenburg
A
A
Woo
S L
SL
Kieback
D G
DG
D000212:Acyclovir / Q000627:therapeutic use* / Q000633:toxicity; D000256:Adenoviridae / Q000235:genetics*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use* / Q000633:toxicity; D015316:Genetic Therapy; D006801:Humans; D010051:Ovarian Neoplasms / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir; D000212:Acyclovir