Combination bacteriolytic therapy for the treatment of experimental tumors

Long H. Dang, Chetan Bettegowda, David L. Huso, Kenneth W Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)15155-15160
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number26
DOIs
StatePublished - Dec 18 2001

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Investigational Therapies
Neoplasms
Spores
Therapeutics
Anaerobic Bacteria
Clostridium
Pharmaceutical Preparations
Necrosis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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abstract = "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.",
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AU - Bettegowda, Chetan

AU - Huso, David L.

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

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