Bacteriolytic Therapy Can Generate a Potent Immune Response against Experimental Tumors

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. Surprisi...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 101; no. 42; pp. 15172 - 15177
Main Authors 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, Abusedera, Mohammad, Wahl, Richard L., Kinzler, Kenneth W., Zhou, Shibin, Huso, David L., Vogelstein, Bert
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 19.10.2004
National Acad Sciences
Subjects
Adoptive Transfer
Animals
Bacteria
Bacterial spores
Bacteriolysis
Biological Sciences
Cell Line, Tumor
Clostridium - immunology
Clostridium Infections - immunology
Clostridium novyi
Cytokines
Experiments
Immune response
Immune system
Inflammation
Lesions
Lymphocytes
Mice
Mice, Inbred BALB C
Models, Immunological
Neoplasms, Experimental - immunology
Neoplasms, Experimental - pathology
Neoplasms, Experimental - therapy
Rabbits
Spores
Spores, Bacterial - immunology
Therapy
Tumors
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Summary: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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To whom correspondence should be addressed. E-mail: vogelbe@jhmi.edu.
Abbreviations: CT, computed tomography; PET, positron emission tomography; FDG, [18F]fluorodeoxyglucose.
C.B. and I.C. contributed equally to this work.
Contributed by Bert Vogelstein, August 25, 2004
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0406242101