• Nicholas J Roberts, Linping Zhang, Filip Janku, Amanda Collins, Ren-Yuan Bai, Verena Staedtke, Anthony W Rusk, David Tung, Maria Miller, Jeffrey Roix, Kristen V Khanna, Ravi Murthy, Robert S Benjamin, Thorunn Helgason, Ariel D Szvalb, Justin E Bird, Sinchita Roy-Chowdhuri, Halle H Zhang, Yuan Qiao, Baktiar Karim, Jennifer McDaniel, Amanda Elpiner, Alexandra Sahora, Joshua Lachowicz, Brenda Phillips, Avenelle Turner, Mary K Klein, Gerald Post, Luis A Diaz, Gregory J Riggins, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Chetan Bettegowda, David L Huso, Mary Varterasian, Saurabh Saha, and Shibin Zhou.
• The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA.
• Sci Transl Med. 2014 Aug 13;6(249):249ra111.

AbstractSpecies 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.Copyright © 2014, American Association for the Advancement of Science.

28 keywords...

hide…