Pharmacologic and toxicologic evaluation of C. novyi-NT spores.
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.
Diaz
Luis A
LA
Howard Hughes Medical Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Cheong
Ian
I
Foss
Catherine A
CA
Zhang
Xiaosong
X
Peters
Brock A
BA
Agrawal
Nishant
N
Bettegowda
Chetan
C
Karim
Baktiar
B
Liu
Guosheng
G
Khan
Khalid
K
Huang
Xin
X
Kohli
Manu
M
Dang
Long H
LH
Hwang
Paul
P
Vogelstein
Ahava
A
Garrett-Mayer
Elizabeth
E
Kobrin
Barry
B
Pomper
Martin
M
Zhou
Shibin
S
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Huso
David L
DL
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
D000972:Antineoplastic Agents, Phytogenic; D001427:Bacterial Toxins