2014年8月19日讯 /生物谷BIOON/--近日，Johns Hopkins和BioMed Valley Discoveries科学家们已经证明，注射细菌--诺维氏芽孢梭菌（Clostridium novyi），可以缩小大鼠和犬体内肿瘤大小。他们的做法更新了19世纪90年代癌症研究人员William Coley的早期工作，Coley注意到有些病人癌症术后发生感染后，病情得到缓解或甚至癌症得到了治愈。
Coley开发了基于杀死细菌的治疗手段，但未能赢得其他同行的相信，他们质疑Coley设计的治疗方法的有效性以及安全性。虽然出发点是提高免疫反应的潜在抗癌好处，其他研究人员也重复Coley的方法在过去几十年，但结果是喜忧参半。
但现在，科学家们公布的结果表明：注入细菌能根除肿瘤组织。该研究结果发表在Science Translational Medicine杂志上。
使用诺维氏芽孢梭菌的优点在于，它只在缺氧环境中“旺盛”，如那些肿瘤组织内部。对于肿瘤组织内部缺乏必要的血液和氧气，传统疗法是不能发挥作用的。但是，缺氧耐受微生物可“挂载”感染并诱发强烈的免疫反应。
在他们的研究中，研究人员引入了多项创新：他们去除了诺维氏芽孢梭菌的毒素生成基因，制造出更安全的C. novyi-NT。他们决定直接注射细菌孢子到肿瘤中，而不是依靠静脉途径。
这是众所周知的，实验模型常常不可靠预测的人类癌症患者对治疗的应答，因此，研究使用自然发生肿瘤的犬作为研究对象。研究人员直接肿瘤注射C. noyvi-NT孢子到16只犬肿瘤部位，其中六只犬第一次治疗后21天有抗肿瘤反应。六只中的三只显示肿瘤完全消除，其他三只犬的肿瘤最长直径长度至少缩小30％。大多数犬经历的副作用有：典型细菌感染如发烧，肿瘤脓肿和炎症。
在这些令人鼓舞成果的基础上，研究人员瘤内注射C. novyi-NT 孢子，治疗晚期平滑肌肉瘤人类患者，结果发现能减少骨内和骨周围的肿瘤。
目前，研究人员正在测试这种新方法的安全性和有效性。虽然这些结果是初步的，但研究人员认为，C. novyi-NT可能成为免疫治疗癌症的新武器。
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Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses
Nicholas J. Roberts,et al.
Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.
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