title: Pharmacologic and toxicologic evaluation of C. novyi-NT spores.
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.
authors.affiliation: Howard Hughes Medical Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: Ian
authors.initials: I
authors.lastname: Cheong
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Zhang
authors.forename: Brock A
authors.initials: BA
authors.lastname: Peters
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
authors.forename: Baktiar
authors.initials: B
authors.lastname: Karim
authors.forename: Guosheng
authors.initials: G
authors.lastname: Liu
authors.forename: Khalid
authors.initials: K
authors.lastname: Khan
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Manu
authors.initials: M
authors.lastname: Kohli
authors.forename: Long H
authors.initials: LH
authors.lastname: Dang
authors.forename: Paul
authors.initials: P
authors.lastname: Hwang
authors.forename: Ahava
authors.initials: A
authors.lastname: Vogelstein
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: Barry
authors.initials: B
authors.lastname: Kobrin
authors.forename: Martin
authors.initials: M
authors.lastname: Pomper
authors.forename: Shibin
authors.initials: S
authors.lastname: Zhou
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: David L
authors.initials: DL
authors.lastname: Huso
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000633:toxicity*; D001427:Bacterial Toxins / Q000493:pharmacokinetics / Q000633:toxicity*; D002460:Cell Line; D003013:Clostridium / Q000254:growth & development / Q000472:pathogenicity*; D004195:Disease Models, Animal; D005260:Female; D007275:Injections, Intravenous; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D013171:Spores, Bacterial / Q000472:pathogenicity*; D015996:Survival Rate
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001427:Bacterial Toxins