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

doi:10.1073/pnas.0406242101

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 language	English (US)
Pages (from-to)	15172-15177
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	42
DOIs	https://doi.org/10.1073/pnas.0406242101
State	Published - Oct 19 2004

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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

Agrawal, N, Bettegowda, C, Cheong, I, Geschwind, JF, Drake, CG, Hipkiss, EL, Tatsumi, M, Dang, LH, Diaz, LA, Pomper, M, Abusedera, M, Wahl, RL, Kinzler, KW , Zhou, S, Huso, DL & 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, vol. 101, no. 42, pp. 15172-15177. https://doi.org/10.1073/pnas.0406242101

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title = "Bacteriolytic therapy can generate a potent immune response against experimental tumors",

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.",

author = "Nishant Agrawal and Chetan Bettegowda and Ian Cheong and Geschwind, {Jean Francois} and Drake, {Charles G.} and Hipkiss, {Edward L.} and Mitsuaki Tatsumi and Dang, {Long H.} and Diaz, {Luis A.} and Martin Pomper and Mohammad Abusedera and Wahl, {Richard L.} and Kinzler, {Kenneth W.} and Shibin Zhou and Huso, {David L.} and Bert Vogelstein",

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doi = "10.1073/pnas.0406242101",

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AU - Agrawal, Nishant

AU - Bettegowda, Chetan

AU - Cheong, Ian

AU - Geschwind, Jean Francois

AU - Drake, Charles G.

AU - Hipkiss, Edward L.

AU - Tatsumi, Mitsuaki

AU - Dang, Long H.

AU - Diaz, Luis A.

AU - Pomper, Martin

AU - Abusedera, Mohammad

AU - Wahl, Richard L.

AU - Kinzler, Kenneth W.

AU - Zhou, Shibin

AU - Huso, David L.

AU - Vogelstein, Bert

PY - 2004/10/19

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AB - 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.

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Bacteriolytic therapy can generate a potent immune response against experimental tumors

Abstract

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