Pharmacologic and toxicologic evaluation of C. novyi-NT spores

Luis A. Diaz, Ian Cheong, Catherine A. Foss, Xiaosong Zhang, Brock A. Peters, Nishant Agrawal, Chetan Bettegowda, Baktiar Karim, Guosheng Liu, Khalid Khan, Xin Huang, Manu Kohli, Long H. Dang, Paul Hwang, Ahava Vogelstein, Elizabeth Garrett-Mayer, Barry Kobrin, Martin Pomper, Shibin Zhou, Kenneth W. KinzlerBert Vogelstein, David L. Huso

Research output: Contribution to journalArticle

Abstract

Clostridium novyi-NT (C. novyi-NT) spores have been shown to be potent therapeutic agents in experimental tumors of mice and rabbits. In the present study, pharmacologic and toxicologic studies were performed to better understand the factors influencing the efficacy and toxicity of this form of therapy. We found that spores were rapidly cleared from the circulation by the reticuloendothelial system. Even after large doses were administered, no clinical toxicity was observed in healthy mice or rabbits. The spores were also not toxic in mice harboring poorly vascularized non-neoplastic lesions, including myocardial infarcts. In tumor-bearing mice, toxicity appeared related to tumor size and spore dose, as expected with any bacterial infection. However, there was no laboratory or histopathologic evidence of sepsis, and the toxicity could be effectively controlled by simple hydration.

Original languageEnglish (US)
Pages (from-to)562-575
Number of pages14
JournalToxicological Sciences
Volume88
Issue number2
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Toxicology

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    Diaz, L. A., Cheong, I., Foss, C. A., Zhang, X., Peters, B. A., Agrawal, N., Bettegowda, C., Karim, B., Liu, G., Khan, K., Huang, X., Kohli, M., Dang, L. H., Hwang, P., Vogelstein, A., Garrett-Mayer, E., Kobrin, B., Pomper, M., Zhou, S., ... Huso, D. L. (2005). Pharmacologic and toxicologic evaluation of C. novyi-NT spores. Toxicological Sciences, 88(2), 562-575. https://doi.org/10.1093/toxsci/kfi316