Combination bacteriolytic therapy for the treatment of experimental tumors
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Combination bacteriolytic therapy for the treatment of experimental tumors
Long H. Dang, Chetan Bettegowda, David L. Huso, Kenneth W. Kinzler, and Bert Vogelstein*
The Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Division of Comparative Medicine, The Johns Hopkins School of Medicine, and The Johns Hopkins Oncology Center, 1650 Orleans Street, Baltimore, MD 21231
Contributed by Bert Vogelstein, October 12, 2001
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. |
