Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex virus G207 by upregulating ribonucleotide reductase

Surgery ◽  
2002 ◽  
Vol 132 (2) ◽  
pp. 353-359 ◽  
Author(s):  
Stephen F. Stanziale ◽  
Henrik Petrowsky ◽  
John K. Joe ◽  
Gretchen D. Roberts ◽  
Jonathan S. Zager ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Ionizing Radiation ◽  
Ribonucleotide Reductase ◽  
Antitumor Efficacy ◽  
Oncolytic Herpes Simplex Virus ◽  
Simplex Virus

Antitumor efficacy of a cytokine secreting, oncolytic herpes simplex virus

2000 ◽  
Vol 191 (4) ◽  
pp. S68-S69
Author(s):  
Sandeep Malhotra ◽  
Joseph Bennett ◽  
Jonathan Zager ◽  
Keith Delman ◽  
Michael Ebright ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antitumor Efficacy ◽  
Oncolytic Herpes Simplex Virus ◽  
Simplex Virus

scholarly journals Functional Interaction between Fluorodeoxyuridine-Induced Cellular Alterations and Replication of a Ribonucleotide Reductase-Negative Herpes Simplex Virus

2001 ◽  
Vol 75 (15) ◽  
pp. 7050-7058 ◽  
Author(s):  
Henrik Petrowsky ◽  
Gretchen D. Roberts ◽  
David A. Kooby ◽  
Bryan M. Burt ◽  
Joseph J. Bennett ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Replication ◽  
Ribonucleotide Reductase ◽  
Oncolytic Herpes Simplex Virus ◽  
Combined Use ◽  
Synergistic Cytotoxicity ◽  
Carboxyl Terminal ◽  
Simplex Virus ◽  
Dependent Mechanism

ABSTRACT G207 is an oncolytic herpes simplex virus (HSV) which is attenuated by inactivation of viral ribonucleotide reductase (RR) and deletion of both γ 1 34.5 genes. The cellular counterparts that can functionally substitute for viral RR and the carboxyl-terminal domain of ICP34.5 are cellular RR and the corresponding homologous domain of the growth arrest and DNA damage protein 34 (GADD34), respectively. Because the thymidylate synthetase (TS) inhibitor fluorodeoxyuridine (FUdR) can alter expression of cellular RR and GADD34, we examined the effect of FUdR on G207 bioactivity with the hypothesis that FUdR-induced cellular changes will alter viral proliferation and cytotoxicity. Replication of wild-type HSV-1 was impaired in the presence of 10 nM FUdR, whereas G207 demonstrated increased replication under the same conditions. Combined use of FUdR and G207 resulted in synergistic cytotoxicity. FUdR exposure caused elevation of RR activity at 10 and 100 nM, whereas GADD34 was induced only at 100 nM. The effect of enhanced viral replication by FUdR was suppressed by hydroxyurea, a known inhibitor of RR. These results demonstrate that the growth advantage of G207 in FUdR-treated cells is primarily based on an RR-dependent mechanism. Although our findings show that TS inhibition impairs viral replication, the FUdR-induced RR elevation may overcome this disadvantage, resulting in enhanced replication of G207. These data provide the cellular basis for the combined use of RR-negative HSV mutants and TS inhibitors in the treatment of cancer.

scholarly journals Antitumor efficacy of oncolytic herpes simplex virus adsorbed onto antigen-specific lymphocytes

2012 ◽  
Vol 19 (4) ◽  
pp. 292-298 ◽  
Author(s):  
A Kanzaki ◽  
H Kasuya ◽  
K Yamamura ◽  
T T Sahin ◽  
N Nomura ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antitumor Efficacy ◽  
Oncolytic Herpes Simplex Virus ◽  
Simplex Virus
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