Zhao Wenbin, Li Yangyang, Liu Wenhui, Ding Ding, Xu Yingchun, Pan Liqiang, Chen Shuqing
College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China.
Hisun Pharma (Hangzhou). CO., LTD., Xialian Village, Xukou Town, Fuyang, Hangzhou 311404, China.
Toxins (Basel). 2016 Jun 16;8(6):185. doi: 10.3390/toxins8060185.
Staphylococcal enterotoxin C2 (SEC2) is a classical superantigen (SAg), which can tremendously activate T lymphocytes at very low dosage, thus exerting its powerful antitumor activity. As an intravenous protein drug and a bacterial toxin, SEC2 has some limitations including poor patient compliance and toxic side effects. In this research, we devoted our attention to studying the antitumor activity and toxicity of SEC2 as a potential oral administration protein drug. We proved that His-tagged SEC2 (SEC2-His) could undergo facilitated transcytosis on human colon adenocarcinoma (Caco-2) cells and SEC2-His was detected in the blood of rats after oral administration. Furthermore, oral SEC2-His caused massive cytokine release and immune cell enrichment around tumor tissue, leading to inhibition of tumor growth in vivo. Meanwhile, although SEC2-His was dosed up to 32 mg/kg in mice, no significant toxicity was observed. These data showed that SEC2 can cross the intestinal epithelium in an immunologically integral form, maintaining antitumor activity but with reduced systemic toxicity. Therefore, these results may have implications for developing SEC2 as an oral administration protein drug.
葡萄球菌肠毒素C2（SEC2）是一种典型的超抗原（SAg），它能够在极低剂量下极大地激活T淋巴细胞，从而发挥其强大的抗肿瘤活性。作为一种静脉注射用蛋白质药物和细菌毒素，SEC2存在一些局限性，包括患者依从性差和毒副作用。在本研究中，我们致力于研究SEC2作为一种潜在的口服蛋白质药物的抗肿瘤活性和毒性。我们证明，带有His标签的SEC2（SEC2-His）能够在人结肠腺癌（Caco-2）细胞上进行易化转胞吞作用，并且在口服给药后在大鼠血液中检测到了SEC2-His。此外，口服SEC2-His导致肿瘤组织周围大量细胞因子释放和免疫细胞富集，从而在体内抑制肿瘤生长。同时，尽管在小鼠中给予高达32 mg/kg的SEC2-His，但未观察到明显的毒性。这些数据表明，SEC2能够以免疫完整的形式穿过肠上皮，保持抗肿瘤活性但全身毒性降低。因此，这些结果可能对将SEC2开发为口服蛋白质药物具有启示意义。
