Hui Jing, Xiao Fang, Li Hui, Cui Xiaojin, Liu Hongsheng, Hu Fengqing
Laboratory of Biomaterials and Biopharmaceuticals, School of Life Sciences, Liaoning University, Shenyang 110036, China.
Sheng Wu Gong Cheng Xue Bao. 2011 Jun;27(6):891-9.
Clinical application of staphylococcal enterotoxin C2 (SEC2) was restricted during the cure of malignant tumor due to its side-effects. The aim of this study was to obtain SEC2 mutant, preserving the important functional sites responsible for the T-cell stimulatory activities but removing the sites responsible for emetic activity, through truncation of SEC2. It would efficiently solve the question of SEC2 side-effect. According to the results of methyl thiazol tetrazolium (MTT) assay in vitro, novel truncated SEC2 mutant (NSM) efficiently stimulated T-cell proliferation and inhibited the growth of such tumor cells as human colorectal cancer cells (Cx-1) and human breast cancer cells (MCF-7) in vitro. Activities of T cell stimulating and anti-tumor of NSM were similar to those of SEC2. According to results of animal experiments, the mutant no longer induced emetic response even if the dose was a 10-fold excess of the amount of SEC2 required. And also, NSM obviously inhibited the tumor growth in tumor-bearing mice. Therefore, we obtained novel truncated staphylococcal enterotoxin C2 mutant, which could efficiently inhibit the growth of tumor cells. It will become novel anti-tumor agents with the lowest side-effects and best treatment effects in clinic.
由于葡萄球菌肠毒素C2(SEC2)的副作用,其在恶性肿瘤治疗中的临床应用受到限制。本研究的目的是通过截短SEC2来获得SEC2突变体,保留负责T细胞刺激活性的重要功能位点,但去除负责催吐活性的位点。这将有效解决SEC2的副作用问题。根据体外甲基噻唑四氮唑(MTT)试验结果,新型截短的SEC2突变体(NSM)能有效刺激T细胞增殖,并在体外抑制人结肠癌细胞(Cx-1)和人乳腺癌细胞(MCF-7)等肿瘤细胞的生长。NSM的T细胞刺激和抗肿瘤活性与SEC2相似。根据动物实验结果,即使剂量比所需的SEC2量高出10倍,该突变体也不再诱导催吐反应。此外,NSM明显抑制荷瘤小鼠的肿瘤生长。因此,我们获得了新型截短的葡萄球菌肠毒素C2突变体,它能有效抑制肿瘤细胞生长。它将成为临床上副作用最小、治疗效果最佳的新型抗肿瘤药物。