An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy

Herpes simplex viruses type 1 (HSV-1) with an inactivated viral ribonucleotide reductase ( Hsrr , ICP6) were designed to target tumor cells with upregulated mammalian ribonucleotide reductase ( mRR ), an enzyme whose expression is regulated by the p16/pRB tumor suppressor pathway. A recombinant HSV-...

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Bibliographic Details
Published in:Bio/technology (New York, N.Y. 1983) N.Y. 1983), 1998-05, Vol.16 (5), p.444-448
Main Authors: Chase, Maureen, Chung, Richard Y, Chiocca, E. Antonio
Format: Article
Language:English
Subjects:
Agriculture
Animals
Antineoplastic agents
Antineoplastic Agents, Alkylating - pharmacology
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Chemotherapy
Cyclophosphamide - pharmacology
Cytochrome P-450 CYP2B1 - genetics
DNA, Viral - chemistry
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic - genetics
Gene therapy
Health. Pharmaceutical industry
Herpesvirus 1, Human - enzymology
Herpesvirus 1, Human - genetics
Humans
Ifosfamide - pharmacology
Industrial applications and implications. Economical aspects
Life Sciences
Medical sciences
Mice
Mice, Nude
Mutation
Pharmacology. Drug treatments
Prodrugs - pharmacology
Rats
Recombinant Proteins - genetics
research-article
Ribonucleotide Reductases - chemistry
Ribonucleotide Reductases - genetics
Tumor Cells, Cultured
Up-Regulation - genetics
Virus Replication - drug effects
Virus Replication - genetics
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Summary:Herpes simplex viruses type 1 (HSV-1) with an inactivated viral ribonucleotide reductase ( Hsrr , ICP6) were designed to target tumor cells with upregulated mammalian ribonucleotide reductase ( mRR ), an enzyme whose expression is regulated by the p16/pRB tumor suppressor pathway. A recombinant HSV-1 was generated by knock-out of Hsrr and insertion of the rat CYP2B1 transgene responsible for the bioactivation of the prodrugs, cyclophosphamide and ifosfamide. The mutant virus replicated selectively in rat and human tumor cells that express mRR. Addition of cyclophosphamide potentiated oncolytic effects against cultured tumor cells and subcutaneous tumor xenografts established in athymic mice.
ISSN:0733-222X
1087-0156
2331-3684
1546-1696
DOI:10.1038/nbt0598-444