Replication-selective herpes simplex virus type 1 mutant therapy of cervical cancer is enhanced by low-dose radiation.

Details

Serval ID
serval:BIB_AA24C7693806
Type
Article: article from journal or magazin.
Collection
Publications
Title
Replication-selective herpes simplex virus type 1 mutant therapy of cervical cancer is enhanced by low-dose radiation.
Journal
Human Gene Therapy
Author(s)
Blank S.V., Rubin S.C., Coukos G., Amin K.M., Albelda S.M., Molnar-Kimber K.L.
ISSN
1043-0342 (Print)
ISSN-L
1043-0342
Publication state
Published
Issued date
2002
Volume
13
Number
5
Pages
627-639
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Abstract
Herpes simplex virus type 1 (HSV-1)-based oncolytic treatment is a promising therapeutic approach for malignancy. Recombinant strains of HSV-1 containing mutations in the ICP 34.5 protein have been shown to replicate preferentially in rapidly proliferating malignant cells, resulting in a direct cytolytic effect. We assessed the efficacy of multimutated HSV-1 strains on human cervical cancer, and then used these viruses in combination with radiation therapy, the standard treatment for cervical cancer. The HSV-1 mutants 4009, 7020, 3616, and G207 induced significant lysis of three established human cervical cancer cell lines in vitro in a dose-dependent manner. G207 intratumoral treatment of established subcutaneous C33a tumors in severe combined immunodeficient (SCID) mice significantly reduced tumor burden by 50%. Weekly and triweekly treatments improved efficacy and inhibited flank tumor growth in an administration frequency-dependent manner without toxicity. Combination therapy of a low dose of radiation (1.5 or 3 Gy) and replication-selective HSV mutants infection exhibited increased antitumor effects against cervical cancer cells in vitro. The in vivo effect of G207 combined with low-dose radiation was studied in Me180 xenografts in athymic mice. Treatment of established Me180 tumor nodules with 3 Gy followed by intratumoral G207 administration greatly improved efficacy, resulting in 42% complete eradication of tumor. In conclusion, single and multiple intratumoral injections of G207 significantly reduced tumor burden in xenogeneic models of cervical cancer, and the addition of low-dose radiation further potentiated the effect. These results suggest that replication-selective HSV-1 mutants may be potent oncolytic agents for the treatment of cervical cancer.
Keywords
Animals, Biological Therapy, Cell Death, Combined Modality Therapy, Female, HeLa Cells, Herpesvirus 1, Human/genetics, Herpesvirus 1, Human/physiology, Humans, Mice, Mice, SCID, Mutation, Radiation Dosage, Radiotherapy, Uterine Cervical Neoplasms/pathology, Uterine Cervical Neoplasms/therapy, Viral Proteins/genetics, Virus Replication/genetics
Pubmed
Web of science
Create date
14/10/2014 11:43
Last modification date
20/08/2019 15:14
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