Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats

Research output: Contribution to journalArticle

Abstract

Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced cancer cell survival and therapy resistance, but also yields a microenvironment that is in many aspects unique within the human body, thus offering potential therapeutic opportunities. The spore-forming anaerobic bacterium Clostridium novyi-NT (C. novyi-NT) has the ability to propagate in tumor-generated hypoxia, leading to oncolysis. Here, we show that intravenously injected spores of C. novyi-NT led to dramatic tumor destructions and significant survival increases in implanted, intracranial syngeneic F98 and human xenograft 060919 rat GBM models. C. novyi-NT germination was specific and confined to the neoplasm, with sparing of the normal brain parenchyma. All animals tolerated the bacteriolytic treatment, but edema and increased intracranial pressure could quickly be lethal if not monitored and medically managed with hydration and antibiotics. These results provide pre-clinical data supporting the development of this therapeutic approach for the treatment of patients with GBM.

Original languageEnglish (US)
Pages (from-to)5536-5546
Number of pages11
JournalOncotarget
Volume6
Issue number8
StatePublished - 2015

Fingerprint

Clostridium
Glioblastoma
Spores
Neoplasms
Anaerobic Bacteria
Intracranial Pressure
Therapeutics
Germination
Cell- and Tissue-Based Therapy
Human Body
Heterografts
Brain Neoplasms
Edema
Cell Survival
Anti-Bacterial Agents
Survival
Brain

Keywords

  • Bacterial therapy
  • Clostridium novyi-NT
  • Glioblastoma multiforme
  • Stroke

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats",
abstract = "Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced cancer cell survival and therapy resistance, but also yields a microenvironment that is in many aspects unique within the human body, thus offering potential therapeutic opportunities. The spore-forming anaerobic bacterium Clostridium novyi-NT (C. novyi-NT) has the ability to propagate in tumor-generated hypoxia, leading to oncolysis. Here, we show that intravenously injected spores of C. novyi-NT led to dramatic tumor destructions and significant survival increases in implanted, intracranial syngeneic F98 and human xenograft 060919 rat GBM models. C. novyi-NT germination was specific and confined to the neoplasm, with sparing of the normal brain parenchyma. All animals tolerated the bacteriolytic treatment, but edema and increased intracranial pressure could quickly be lethal if not monitored and medically managed with hydration and antibiotics. These results provide pre-clinical data supporting the development of this therapeutic approach for the treatment of patients with GBM.",
keywords = "Bacterial therapy, Clostridium novyi-NT, Glioblastoma multiforme, Stroke",
author = "Verena Staedtke and Renyuan Bai and Weiyun Sun and Judy Huang and Kibler, {Kathleen Kazuko} and Tyler, {Betty Mae} and Gallia, {Gary L} and Kinzler, {Kenneth W} and Bert Vogelstein and Shibin Zhou and Riggins, {Gregory J}",
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AU - Staedtke, Verena

AU - Bai, Renyuan

AU - Sun, Weiyun

AU - Huang, Judy

AU - Kibler, Kathleen Kazuko

AU - Tyler, Betty Mae

AU - Gallia, Gary L

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - Zhou, Shibin

AU - Riggins, Gregory J

PY - 2015

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N2 - Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced cancer cell survival and therapy resistance, but also yields a microenvironment that is in many aspects unique within the human body, thus offering potential therapeutic opportunities. The spore-forming anaerobic bacterium Clostridium novyi-NT (C. novyi-NT) has the ability to propagate in tumor-generated hypoxia, leading to oncolysis. Here, we show that intravenously injected spores of C. novyi-NT led to dramatic tumor destructions and significant survival increases in implanted, intracranial syngeneic F98 and human xenograft 060919 rat GBM models. C. novyi-NT germination was specific and confined to the neoplasm, with sparing of the normal brain parenchyma. All animals tolerated the bacteriolytic treatment, but edema and increased intracranial pressure could quickly be lethal if not monitored and medically managed with hydration and antibiotics. These results provide pre-clinical data supporting the development of this therapeutic approach for the treatment of patients with GBM.

AB - Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced cancer cell survival and therapy resistance, but also yields a microenvironment that is in many aspects unique within the human body, thus offering potential therapeutic opportunities. The spore-forming anaerobic bacterium Clostridium novyi-NT (C. novyi-NT) has the ability to propagate in tumor-generated hypoxia, leading to oncolysis. Here, we show that intravenously injected spores of C. novyi-NT led to dramatic tumor destructions and significant survival increases in implanted, intracranial syngeneic F98 and human xenograft 060919 rat GBM models. C. novyi-NT germination was specific and confined to the neoplasm, with sparing of the normal brain parenchyma. All animals tolerated the bacteriolytic treatment, but edema and increased intracranial pressure could quickly be lethal if not monitored and medically managed with hydration and antibiotics. These results provide pre-clinical data supporting the development of this therapeutic approach for the treatment of patients with GBM.

KW - Bacterial therapy

KW - Clostridium novyi-NT

KW - Glioblastoma multiforme

KW - Stroke

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