期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 6, 期 249, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3008982
关键词
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资金
- BioMed Valley Discoveries Inc.
- Virginia and D.K. Ludwig Fund
- Maryland Cigarette Restitution Fund
- Commonwealth Fund
- Swim Across America
- Burroughs Wellcome Career Awards
- Voices Against Brain Cancer
- Sol Goldman Pancreatic Cancer Research Center
- Johns Hopkins Clinician Scientist Award
- NIH [CA129825, CA062924]
- National Institute of Neurological Disorders and Stroke [R25NS065729]
Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.
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