Systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice

Yunpeng Su, Janelle Ortiz, Shihui Liu, Thomas H. Bugge, Ravibhushan Singh, Stephen H. Leppla, Arthur E. Frankel

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The novel recombinant anthrax toxin, PrAgU2/FP59, composed of the urokinase-activated protective antigen and a fusion protein of Pseudomonas exotoxin and lethal factor was tested for anti-lung cancer efficacy in an in vivo human tumor model. Male athymic nude mice (age 4-6 weeks) were inoculated s.c. with 10 million H1299 non-small cell lung cancer (NSCLC) cells in the left flank. When tumor volumes reached 200 mm3 (6-8 days), i.p. injection of 100 μL saline or different ratios and doses of PrAgU2/FP59 in 100 μL saline were given every 3 days for four doses and an additional dose at day 29. Animals were monitored twice daily and tumor measurements were made by calipers. The maximum tolerated doses of PrAgU2/FP59 differed dependent on the ratios of PrAgU2 to FP59 over the range of 3:1 to 25:1, respectively. At tolerated doses, tumor regressions were seen in all animals. Complete histologic remission lasting 60 days occurred in 30% of animals. PrAgU2/FP59 showed dramatic anti-NSCLC efficacy and warrants further clinical development for therapy of patients with advanced NSCLC.

Original languageEnglish (US)
Pages (from-to)3329-3336
Number of pages8
JournalCancer research
Volume67
Issue number7
DOIs
StatePublished - Apr 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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