Johns Hopkins University2014-11-21 4:34 PM

Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses

Abstract


Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments . We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise , tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection . 


It is well known , however , that experimental models often do not reliably predict the responses of human patients to therapeutic agents . We therefore used naturally occurring canine tumors as a translational bridge to human trials . 


Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds , are of host origin, and are due to spontaneous rather than engineered mutations . We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors , with the most common toxicities being the expected symptoms associated with bacterial infections . 


Objective responses were observed in 6 of 16 dogs (37.5%) , with three complete and three partial responses . On the basis of these encouraging results , we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores . This treatment reduced the tumor within and surrounding the bone . Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted .


Full Article:

http://stm.sciencemag.org/content/6/249/249ra111.abstract

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