Su Yunpeng, Ortiz Janelle, Liu Shihui, Bugge Thomas H, Singh Ravibhushan, Leppla Stephen H, Frankel Arthur E
Cancer Research Institute, Scott & White Memorial Hospital, Temple, Texas, USA.
Cancer Res. 2007 Apr 1;67(7):3329-36. doi: 10.1158/0008-5472.CAN-06-4642.
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.
新型重组炭疽毒素PrAgU2/FP59由尿激酶激活的保护性抗原以及铜绿假单胞菌外毒素与致死因子的融合蛋白组成，在人源肿瘤体内模型中对其抗肺癌疗效进行了测试。4至6周龄的雄性无胸腺裸鼠在左腹侧皮下接种1000万个H1299非小细胞肺癌（NSCLC）细胞。当肿瘤体积达到200立方毫米（6至8天）时，每3天腹腔注射100微升生理盐水或100微升含不同比例和剂量PrAgU2/FP59的生理盐水，共注射四剂，并在第29天额外注射一剂。每天对动物进行两次监测，并用卡尺测量肿瘤大小。PrAgU2/FP59的最大耐受剂量因PrAgU2与FP59的比例分别在3:1至25:1范围内而有所不同。在耐受剂量下，所有动物的肿瘤均出现消退。30%的动物出现了持续60天的完全组织学缓解。PrAgU2/FP59显示出显著的抗NSCLC疗效，值得进一步开展针对晚期NSCLC患者治疗的临床研究。
