An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy
- 1 May 1998
- journal article
- research article
- Published by Springer Nature in Nature Biotechnology
- Vol. 16 (5) , 444-448
- https://doi.org/10.1038/nbt0598-444
Abstract
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.Keywords
This publication has 23 references indexed in Scilit:
- The Effect of Ganciclovir on Herpes Simplex Virus-Mediated OncolysisJournal of Surgical Research, 1997
- A Novel Multiply-Mutated HSV-1 Strain for the Treatment of Human Brain TumorsHuman Gene Therapy, 1997
- An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor CellsScience, 1996
- Retrovirus–mediated wild–type P53 gene transfer to tumors of patients with lung cancer.Nature Medicine, 1996
- Attenuated multi–mutated herpes simplex virus–1 for the treatment of malignant gliomasNature Medicine, 1995
- Complete Regression of Human Neuroblastoma Xenografts in Athymic Mice After Local Newcastle Disease Virus TherapyJNCI Journal of the National Cancer Institute, 1994
- Experimental Tumor Therapy in Mice Using the Cyclophosphamide-Activating Cytochrome P450 2B1 GeneHuman Gene Therapy, 1994
- Differential regulation of E2F transactivation by cyclin/cdk2 complexes.Genes & Development, 1994
- Retrovirally TransducedEscherichia coli gptGenes Combine Selectability with Chemosensitivity Capable of Mediating Tumor EradicationHuman Gene Therapy, 1993
- Clonal expansion of p53 mutant cells is associated with brain tumour progressionNature, 1992