Department of General, Vascular, Thoracic and Transplantation Surgery, Section of Molecular Oncology and Immunotherapy, University of Rostock, 18057 Rostock, Germany.
World J Gastroenterol. 2010 Jul 28;16(28):3546-52. doi: 10.3748/wjg.v16.i28.3546.
To investigate the effectiveness of Clostridium novyi (C. novyi)-NT spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic, immunocompetent Panc02/C57Bl/6 model.
C. novyi-NT spores were applied intravenously to animals carrying established pancreatic tumors of three different sizes. Systemic immune responses in peripheral blood and spleen were examined by flow cytometry. Supplementary, cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed.
Application of spores identified, that (1) small tumors (< 150 mm(3)) were completely unaffected (n = 10); (2) very large tumors (> 450 mm(3)) responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n = 6); and (3) an optimal treatment window exists for tumors of approximately 250 mm(3) (n = 21). In this latter group, all tumor-bearing animals had complete tumor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed (tumor volume at day 28: 197.8 +/- 87.3 mm(3) vs 500.1 +/- 50.9 mm(3), P < 0.05). These effects were accompanied by systemic activation of immune response mechanisms predominantly mediated by the innate arm of the immune system.
The observed complete tumor regression is encouraging and shows that immunotherapy with C. novyi-NT is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes.
研究新型诺维梭菌（C. novyi）孢子对同基因免疫活性 Panc02/C57Bl/6 模型中已建立的皮下胰腺肿瘤的治疗效果。
将新型诺维梭菌孢子静脉内应用于携带三种不同大小已建立的胰腺肿瘤的动物。通过流式细胞术检测外周血和脾脏中的全身免疫反应。分析淋巴细胞对同种肿瘤靶标的细胞毒性活性。
应用孢子发现：（1）小肿瘤（<150mm³）完全不受影响（n=10）；（2）非常大的肿瘤（>450mm³）则表现出大量坏死，随后肿瘤缩小，并且由于肿瘤溶解综合征而导致明显的致死性（n=6）；（3）对于大约 250mm³的肿瘤存在最佳的治疗窗口（n=21）。在后一组中，所有荷瘤动物的肿瘤完全消退，并且无肿瘤复发。在随后的肿瘤再攻击实验中，与初始肿瘤细胞接种相比，观察到肿瘤生长明显延迟（肿瘤体积在第 28 天：197.8±87.3mm³比 500.1±50.9mm³，P<0.05）。这些作用伴随着主要由免疫系统的先天部分介导的全身免疫反应机制的系统激活。
观察到的完全肿瘤消退令人鼓舞，并表明新型诺维梭菌-NT 的免疫疗法是治疗特定大小的胰腺癌的一种有趣策略。
