Imani Fooladi A A, Sattari M, Reza Nourani M
Research Centers of Molecular Biology, Baqiyatallah University of Medical Sciences, Tehran, 3456-445, Iran.
J BUON. 2010 Apr-Jun;15(2):340-7.
Staphylococcal enterotoxin B (SEB) is a potent inducer of cytotoxic T-cell activity, cytokine production and necrosis induction in vivo. Monophosphoryl lipid A (MPL) is an adjuvant derived from the lipopolysaccharide of E. coli, Salmonella Minnesota Re595 and other gram negative bacteria. We investigated the possibility of the therapeutic application of SEB+ MPL in mice with fibrosarcoma.
The antitumor effect of SEB+MPL, SEB and MPL in mice with inoculated fibrosarcoma tumor (WEHI-164) was examined by intravenous (i.v.) and intratumoral (i.t.) injection and the sizes of the inoculated tumors, IFN-gamma production, and CD4(+)/CD8(+) T cell infiltration were determined. The inoculated tumors were also examined histologically.
In the i.v.-injected group of mice with SEB+ MPL, reduction of tumor size showed a significant difference compared with mice in the i.t., the i.v. (MPL)-injected groups and the negative control group (p < 0.02). Moreover, the mice in the i.v. (SEB+ MPL)-injected group showed significantly higher levels of IFN-gamma (p < 0.009) and CD4(+)/CD8(+) T cell infiltration when compared with the other groups (p < 0.02). A significantly higher frequency of necrosis in tumor tissues was also observed in mice in the i.v. (SEB+ MPL)-injected group in comparison with other groups (p < 0.009).
Our findings suggest that tumor cell death is caused by increased cytotoxic T-cell activity, cytokine levels, in response to IV injection of SEB+MPL. They also suggest that tumor cell death by synergistic effect of one of the strongest bacterial superantigens (SEB) with monophosphoryl lipid A and SEB+MPL may be a good option for use as a novel therapy in patients with fibrosarcoma.
葡萄球菌肠毒素B（SEB）是体内细胞毒性T细胞活性、细胞因子产生和坏死诱导的强效诱导剂。单磷酰脂质A（MPL）是一种源自大肠杆菌、明尼苏达沙门氏菌Re595和其他革兰氏阴性菌脂多糖的佐剂。我们研究了SEB + MPL在患有纤维肉瘤的小鼠中的治疗应用可能性。
通过静脉内（i.v.）和瘤内（i.t.）注射，检测SEB + MPL、SEB和MPL对接种纤维肉瘤肿瘤（WEHI - 164）的小鼠的抗肿瘤作用，并测定接种肿瘤的大小、IFN - γ产生以及CD4(+)/CD8(+) T细胞浸润情况。还对接种肿瘤进行了组织学检查。
在静脉注射SEB + MPL的小鼠组中，与瘤内注射组、静脉注射（MPL）组和阴性对照组相比，肿瘤大小的减小显示出显著差异（p < 0.02）。此外，与其他组相比，静脉注射（SEB + MPL）组的小鼠显示出显著更高水平的IFN - γ（p < 0.009）和CD4(+)/CD8(+) T细胞浸润（p < 0.02）。与其他组相比，静脉注射（SEB + MPL）组的小鼠肿瘤组织中坏死频率也显著更高（p < 0.009）。
我们的研究结果表明，静脉注射SEB + MPL后，细胞毒性T细胞活性增加和细胞因子水平升高导致肿瘤细胞死亡。它们还表明，最强的细菌超抗原之一（SEB）与单磷酰脂质A协同作用导致肿瘤细胞死亡，SEB + MPL可能是纤维肉瘤患者新型治疗的良好选择。
