Oncotarget

Priority Research Papers:

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

Verena Staedtke, Ren-Yuan Bai, Weiyun Sun, Judy Huang, Kathleen Kazuko Kibler, Betty M. Tyler, Gary L. Gallia, Kenneth Kinzler, Bert Vogelstein, Shibin Zhou, Gregory J. Riggins _

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Oncotarget. 2015; 6:5536-5546. https://doi.org/10.18632/oncotarget.3627

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Abstract

Verena Staedtke1,*, Ren-Yuan Bai1,*, Weiyun Sun1, Judy Huang1, Kathleen Kazuko Kibler3, Betty M. Tyler1, Gary L. Gallia1, Kenneth Kinzler2, Bert Vogelstein2, Shibin Zhou2 and Gregory J. Riggins1

1 Department of Neurology & Neurosurgery, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

2 Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

3 Department of Pediatrics-Anesthesiology, Baylor College of Medicine, Houston, TX, USA

* These authors contributed equally to this work

Correspondence to:

Gregory J. Riggins, email:

Keywords: Clostridium novyi-NT, bacterial therapy, glioblastoma multiforme, stroke

Received: February 11, 2015 Accepted: February 12, 2015 Published: March 18, 2015

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.


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