Details

Autor(en) / Beteiligte

• Roberts, Nicholas J
• Zhang, Linping
• Janku, Filip
• Collins, Amanda
• Bai, Ren-Yuan
• Staedtke, Verena
• Rusk, Anthony W
• Tung, David
• Miller, Maria
• Roix, Jeffrey
• Khanna, Kristen V
• Murthy, Ravi
• Benjamin, Robert S
• Helgason, Thorunn
• Szvalb, Ariel D
• Bird, Justin E
• Roy-Chowdhuri, Sinchita
• Zhang, Halle H
• Qiao, Yuan
• Karim, Baktiar
• McDaniel, Jennifer
• Elpiner, Amanda
• Sahora, Alexandra
• Lachowicz, Joshua
• Phillips, Brenda
• Turner, Avenelle
• Klein, Mary K
• Post, Gerald
• Diaz, Jr, Luis A
• Riggins, Gregory J
• Papadopoulos, Nickolas
• Kinzler, Kenneth W
• Vogelstein, Bert
• Bettegowda, Chetan
• Huso, David L
• Varterasian, Mary
• Saha, Saurabh
• Zhou, Shibin

Titel

Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses

Ist Teil von

• Science translational medicine, 2014-08, Vol.6 (249), p.249ra111

Ort / Verlag

United States

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.