Bacteriolytic therapy can generate a potent immune response against experimental tumors
Bacteriolytic therapy can generate a potent immune response against experimental tumors
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DOI：
10.1073/pnas.0406242101
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发表时间：
2004-10-19
影响因子：
11.1
通讯作者：
Vogelstein, B
中科院分区：
文献类型：
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作者：
Agrawal, N;Bettegowda, C;Vogelstein, B
当厌氧细菌诺氏梭菌-NT的孢子被全身注射到动物体内时，它们只在癌症的缺氧区域内发芽。发芽的细菌破坏邻近的肿瘤细胞，但保留了一圈氧合良好的肿瘤细胞，这些细胞随后扩张。令人惊讶的是，我们发现，尽管孢子萌发后最初仍保留有存活的肿瘤边缘，但用这种孢子治疗的小鼠中约有30%的癌症治愈。这种效应的机制被证明是免疫介导的，因为治愈的动物拒绝了同一肿瘤的后续挑战。在患有肝内肿瘤的兔中观察到类似的效果。特别值得注意的是，当与诺氏梭菌-NT的溶菌作用组合时，诱导的免疫应答可以根除大的已建立的肿瘤。
When spores of the anaerobic bacterium Clostridium novyi-NT are systemically injected into animals, they germinate exclusively within the hypoxic regions of cancers. The germinated bacteria destroy adjacent tumor cells but spare a rim of well oxygenated tumor cells that subsequently expand. Surprisingly, we found that approximate to30% of mice treated with such spores were cured of their cancers despite the viable tumor rim initially remaining after spore germination. The mechanism underlying this effect was shown to be immune-mediated, because cured animals rejected a subsequent challenge of the same tumor. Similar effects were observed in rabbits with intrahepatic tumors. It was particularly notable that the induced immune response, when combined with the bacteriolytic effects of C novyi-NT, could eradicate large established tumors.