Thurman G B, Russel B A, York G E, Wang Y F, Page D L, Sundell H W, Hellerqvist C G
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Cancer Res Clin Oncol. 1994;120(8):479-84. doi: 10.1007/BF01191801.
GBS toxin is a polysaccharide exotoxin produced by group B Streptococcus. This organism causes sepsis and respiratory distress in human neonates (so-called early onset disease). This disease is marked by a strong inflammatory response only in the lung, with pulmonary sequestration of granulocytes and extensive capillary endothelial damage, and occurs only during the first few days after birth. We have found that a similar inflammatory response can be induced by i.v. infusion of picomole quantities of GBS toxin in the developing vasculature of transplanted tumors in mice and can significantly retard the tumor growth. When optimum treatment with GBS toxin was started shortly after tumor implantation, a majority of tumors in the mice regressed and the mice remained tumor-free for over 5 months. Some tumors regressed in mice receiving short-term treatment with GBS toxin, but recurred after the treatment was stopped. Median survival times were extended by all regimens and all doses of GBS toxin tested. No evidence of toxicity to the vasculature of other tissues was observed. GBS toxin is being tested for cancer therapy in humans.
B族链球菌(GBS)毒素是一种由B组链球菌产生的多糖外毒素。这种微生物会导致人类新生儿败血症和呼吸窘迫(即所谓的早发型疾病)。这种疾病的特征是仅在肺部出现强烈的炎症反应,伴有粒细胞在肺部的聚集和广泛的毛细血管内皮损伤,且仅在出生后的头几天发生。我们发现,通过静脉注射皮摩尔量的GBS毒素,可在小鼠移植肿瘤的发育血管系统中诱导出类似的炎症反应,并能显著延缓肿瘤生长。在肿瘤植入后不久开始用GBS毒素进行最佳治疗时,大多数小鼠体内的肿瘤会消退,并且小鼠在超过5个月的时间内都没有肿瘤。一些接受GBS毒素短期治疗的小鼠体内肿瘤消退,但在治疗停止后复发。所有测试的GBS毒素治疗方案和剂量均延长了中位生存时间。未观察到对其他组织血管系统有毒性的证据。目前正在对GBS毒素进行人体癌症治疗试验。