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Systematic Urokinase-Activated Anthrax Toxin Therapy Produces Regressions of Subcutaneous Human Non–Small Cell Lung Tumor in Athymic Nude Mice

¹ Cancer Research Institute, Scott & White Memorial Hospital, Temple, Texas; and ² Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases; ³ Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, Bethesda, Maryland

Requests for reprints: Arthur E. Frankel, Cancer Research Institute, Scott & White Memorial Hospital, 5701 South Airport Road, Temple, TX 76502. Phone: 254-724-9786; E-mail: afrankel{at}swmail.sw.org.

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. [Cancer Res 2007;67(7):3329–36]