Intraneoplastic polymer-based delivery of cyclophosphamide for intratumoral bioconconversion by a replicating oncolytic viral vector

Tomotsugu Ichikawa, William P. Petros, Susan M. Ludeman, Jim Fangmeier, Fred H. Hochberg, O. Michael Colvin, E. Antonio Chiocca

研究成果査読

45 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)864-868
ページ数5
ジャーナルCancer Research
61
3
出版ステータスPublished - 2月 1 2001
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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