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

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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.

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Authors and Affiliations

  1. Molecular Neuro-oncology Laboratories, Neurosurgical Service, Massachusetts General Hospital-CNY6, Harvard Medical School, Charlestown, MA, 02129

    Maureen Chase, Richard Y. Chung & E. Antonio Chiocca

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  1. Maureen Chase
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  2. Richard Y. Chung
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  3. E. Antonio Chiocca
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Correspondence to E. Antonio Chiocca.

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Chase, M., Chung, R. & Chiocca, E. An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy. Nat Biotechnol 16, 444–448 (1998). https://doi.org/10.1038/nbt0598-444

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