Abstract
rRp450 is an oncolytic herpesvirus that expresses the CYP2B1 cDNA, responsible for bioconverting cyclophosphamide (CPA) into the active metabolites 4-hydroxyCPA/aldophosphamide (AP). However, formal proof of prodrug activation is lacking. We report that activation of CPA in cells infected with rRp450 generates a time-dependent increase of diffusible 4-hydroxyCPA/AP. For in vivo applications, a CPA-impregnated polymer was implanted into human tumor xenografts inoculated with rRp450. The area under the curve for 4-hydroxyCPA/AP was 806 μg/g of tumor tissue/h when CPA was administered via intraneoplastic polymer and 3 μg/g of tumor tissue/h when CPA was administered i.p. Therefore, (a) a lyric virus expressing a “suicide” gene can activate a prodrug; and (b) within rRp450-infected tumor, more prolonged and higher concentrations of activated metabolites are generated by intraneoplastic compared with systemic administration of prodrug.
Original language | English |
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Pages (from-to) | 864-868 |
Number of pages | 5 |
Journal | Cancer Research |
Volume | 61 |
Issue number | 3 |
Publication status | Published - Feb 1 2001 |
ASJC Scopus subject areas
- Oncology
- Cancer Research