期刊
ONCOTARGET
卷 6, 期 8, 页码 5536-5546出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3627
关键词
Clostridium novyi-NT; bacterial therapy; glioblastoma multiforme; stroke
资金
- BioMed Valley Discoveries Inc.
- Children's Cancer Foundation
- Virginia and D. K. Ludwig Fund for Cancer Research
- Voices Against Brain Cancer
- NIH [CA062924]
- National Institute of Neurological Disorders and Stroke [R25NS065729]
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.
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