Combination bacteriolytic therapy for the treatment of experimental tumors
Combination bacteriolytic therapy for the treatment of experimental tumors
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DOI：
10.1073/pnas.251543698
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发表时间：
2001-12-18
影响因子：
11.1
通讯作者：
Vogelstein, B
中科院分区：
文献类型：
--
作者：
Dang, LH;Bettegowda, C;Vogelstein, B
目前用于癌症的化学治疗方法部分地受限于药物不能破坏肿瘤的血管化差的区室中的肿瘤细胞。我们在这里系统地评估了厌氧菌在移植肿瘤无血管区室中扩张生长的能力。在测试的26种不同菌株中，有一种（诺氏梭菌）似乎特别有希望。我们创造了一个C菌株。novyi无致死毒素（C. novyi-NT），并显示静脉注射C.诺氏-NT孢子在小鼠肿瘤的无血管区域内萌发并破坏周围的活肿瘤细胞。当C.诺维-NT孢子与常规化疗药物一起给药，肿瘤的广泛出血性坏死通常在24小时内发展，导致显著和延长的抗肿瘤作用。这种被称为联合溶菌疗法（COBALT）的策略有可能为癌症治疗增加一个新的维度。
Current chemotherapeutic approaches for cancer are in part limited by the inability of drugs to destroy neoplastic cells within poorly vascularized compartments of tumors. We have here systematically assessed anaerobic bacteria for their capacity to grow expansively within avascular compartments of transplanted tumors. Among 26 different strains tested, one (Clostridium novyi) appeared particularly promising. We created a strain of C. novyi devoid of its lethal toxin (C. novyi-NT) and showed that intravenously injected C. novyi-NT spores germinated within the avascular regions of tumors in mice and destroyed surrounding viable tumor cells. When C. novyi-NT spores were administered together with conventional chemotherapeutic drugs, extensive hemorrhagic necrosis of tumors often developed within 24 h, resulting in significant and prolonged antitumor effects. This strategy, called combination bacteriolytic therapy (COBALT), has the potential to add a new dimension to the treatment of cancer.