Systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice.
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 mm(3) (6-8 days), i.p. injection of 100 muL saline or different ratios and doses of PrAgU2/FP59 in 100 muL 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.
Su
Yunpeng
Y
Cancer Research Institute, Scott & White Memorial Hospital, Temple, Texas, USA.
Ortiz
Janelle
J
Liu
Shihui
S
Bugge
Thomas H
TH
Singh
Ravibhushan
R
Leppla
Stephen H
SH
Frankel
Arthur E
AE
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology* / Q000633:toxicity; D001427:Bacterial Toxins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005098:Exotoxins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D005098:Exotoxins; D011993:Recombinant Fusion Proteins; C030325:anthrax toxin; D014568:Urokinase-Type Plasminogen Activator