Combined effects of adeno-associated virus vector and a herpes simplex virus mutant as neoplastic therapy.
OBJECTIVE
Although surgical therapy for pancreatic cancer has not been successful, new gene therapies, such as adeno-associated virus (AAV) vectors hold promise for treating cancer. However, expression of AAV vectors alone is insufficient for adequate effects in vivo for cancer therapy. We describe a novel therapy using the combined herpes simplex virus-ICP6 deletion mutant (ICP6delta) and AAV vector.


METHODS
We investigated ICP6delta and AAV regarding kinetics and dose-response relationships of LacZ expression in vitro. We studied the expression of LacZ in vivo using subcutaneous pancreatic cancer tumors (SW1990) in nude mice.


RESULTS
In vitro, ICP6delta enhanced the expression of AAV; 24 hr following inoculation there was more expression with AAV plus ICP6delta than with AAV plus KOS, and a multiplicity of infection (MOI) of 0.5 was the optimal titer of ICP6delta to support maximal expression of AAV. In vivo, there was much higher expression of LacZ in mice injected with AAV-LacZ plus ICP6A than with AAV-LacZ alone.


CONCLUSIONS
ICP6delta enhances expression of AAV-vector in vitro and in vivo. These results suggested that combined therapy have potential for human cancer.
Kasuya
H
H
Department of Surgery II, Nagoya University School of Medicine, Japan.
Mizuno
M
M
Yoshida
J
J
Nishiyama
Y
Y
Nomoto
S
S
Nakao
A
A
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D012264:Ribonucleotide Reductases / Q000172:deficiency / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D014407:Tumor Cells, Cultured
D012264:Ribonucleotide Reductases