Bacteriolytic therapy can generate a potent immune response against experimental tumors
- Nishant Agrawal*,†,‡,
- Chetan Bettegowda*,†,§,
- Ian Cheong*,†,§,
- Jean-Francois Geschwind¶,
- Charles G. Drake†,
- Edward L. Hipkiss†,
- Mitsuaki Tatsumi¶,
- Long H. Dang*,†,
- Luis A. Diaz, Jr.*,†,
- Martin Pomper¶,
- Mohammad Abusedera¶,
- Richard L. Wahl¶,
- Kenneth W. Kinzler*,†,
- Shibin Zhou*,†,
- David L. Huso∥, and
- Bert Vogelstein*,†,**
- *Howard Hughes Medical Institute, †Sidney Kimmel Cancer Center, and Departments of ‡Otolaryngology-Head and Neck Surgery, ¶Radiology and Radiological Sciences, and ∥Comparative Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231
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Contributed by Bert Vogelstein, August 25, 2004
Abstract
When spores of the anaerobic bacterium Clostridium novyi-NT are systemically injected into animals, they germinate exclusively within the hypoxic regions of cancers. The germinated bacteria destroy adjacent tumor cells but spare a rim of well oxygenated tumor cells that subsequently expand. Surprisingly, we found that ≈30% of mice treated with such spores were cured of their cancers despite the viable tumor rim initially remaining after spore germination. The mechanism underlying this effect was shown to be immune-mediated, because cured animals rejected a subsequent challenge of the same tumor. Similar effects were observed in rabbits with intrahepatic tumors. It was particularly notable that the induced immune response, when combined with the bacteriolytic effects of C. novyi-NT, could eradicate large established tumors.
Footnotes
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↵ ** To whom correspondence should be addressed. E-mail: vogelbe{at}jhmi.edu.
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↵ § C.B. and I.C. contributed equally to this work.
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Abbreviations: CT, computed tomography; PET, positron emission tomography; FDG, [18F]fluorodeoxyglucose.
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Freely available online through the PNAS open access option.
- Copyright © 2004, The National Academy of Sciences
