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, Martin Pomper, Mohammad Abusedera, Richard L. Wahl, Kenneth W. Kinzler, Shibin Zhou, David L. Huso, Bert Vogelstein

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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.

Original languageEnglish (US)
Pages (from-to)15172-15177
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number42
DOIs
StatePublished - Oct 19 2004

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Cite this

Agrawal, N., Bettegowda, C., Cheong, I., Geschwind, J. F., Drake, C. G., Hipkiss, E. L., Tatsumi, M., Dang, L. H., Diaz, L. A., Pomper, M., Abusedera, M., Wahl, R. L., Kinzler, K. W., Zhou, S., Huso, D. L., & Vogelstein, B. (2004). Bacteriolytic therapy can generate a potent immune response against experimental tumors. Proceedings of the National Academy of Sciences of the United States of America, 101(42), 15172-15177. https://doi.org/10.1073/pnas.0406242101