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

Research output: Contribution to journalArticle

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

Fingerprint

Neoplasms
Spores
Therapeutics
Anaerobic Bacteria
Clostridium
Germination
Rabbits
Bacteria

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Bacteriolytic therapy can generate a potent immune response against experimental tumors. / Agrawal, Nishant; Bettegowda, Chetan; Cheong, Ian; Geschwind, Jean Francois; Drake, Charles G.; Hipkiss, Edward L.; Tatsumi, Mitsuaki; Dang, Long H.; Diaz, Luis A.; Pomper, Martin Gilbert; Abusedera, Mohammad; Wahl, Richard L.; Kinzler, Kenneth W; Zhou, Shibin; Huso, David L.; Vogelstein, Bert.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 42, 19.10.2004, p. 15172-15177.

Research output: Contribution to journalArticle

Agrawal, Nishant ; Bettegowda, Chetan ; Cheong, Ian ; Geschwind, Jean Francois ; Drake, Charles G. ; Hipkiss, Edward L. ; Tatsumi, Mitsuaki ; Dang, Long H. ; Diaz, Luis A. ; Pomper, Martin Gilbert ; Abusedera, Mohammad ; Wahl, Richard L. ; Kinzler, Kenneth W ; Zhou, Shibin ; Huso, David L. ; Vogelstein, Bert. / Bacteriolytic therapy can generate a potent immune response against experimental tumors. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 42. pp. 15172-15177.
@article{87ec65f81a324f3eafe83104ad83902f,
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 Pomper, {Martin Gilbert} and Mohammad Abusedera and Wahl, {Richard L.} and Kinzler, {Kenneth W} and Shibin Zhou and Huso, {David L.} and Bert Vogelstein",
year = "2004",
month = "10",
day = "19",
doi = "10.1073/pnas.0406242101",
language = "English (US)",
volume = "101",
pages = "15172--15177",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "42",

}

TY - JOUR

T1 - Bacteriolytic therapy can generate a potent immune response against experimental tumors

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 Gilbert

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

Y1 - 2004/10/19

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=6344284114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6344284114&partnerID=8YFLogxK

U2 - 10.1073/pnas.0406242101

DO - 10.1073/pnas.0406242101

M3 - Article

VL - 101

SP - 15172

EP - 15177

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 42

ER -