Bacteriolytic therapy can generate a potent immune response against experimental tumors

被引:225
作者
Agrawal, N
Bettegowda, C
Cheong, I
Geschwind, JF
Drake, CG
Hipkiss, EL
Tatsumi, M
Dang, LH
Diaz, LA
Pomper, M
Abusedera, M
Wahl, RL
Kinzler, KW
Zhou, SB
Huso, DL
Vogelstein, B [1 ]
机构
[1] Johns Hopkins Med Inst, Howard Hughes Med Inst, Baltimore, MD 21231 USA
[2] Johns Hopkins Med Inst, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA
[3] Johns Hopkins Med Inst, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21231 USA
[4] Johns Hopkins Med Inst, Dept Radiol & Radiol Sci, Baltimore, MD 21231 USA
[5] Johns Hopkins Med Inst, Dept Comparat Med, Baltimore, MD 21231 USA
关键词
D O I
10.1073/pnas.0406242101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
When spores of the anaerobic bacterium Clostridium novyi-NT are systemically injected into animals, they germinate exclusively within the hypoxic regions of cancers. The germinated bacteria destroy adjacent tumor cells but spare a rim of well oxygenated tumor cells that subsequently expand. Surprisingly, we found that approximate to30% of mice treated with such spores were cured of their cancers despite the viable tumor rim initially remaining after spore germination. The mechanism underlying this effect was shown to be immune-mediated, because cured animals rejected a subsequent challenge of the same tumor. Similar effects were observed in rabbits with intrahepatic tumors. It was particularly notable that the induced immune response, when combined with the bacteriolytic effects of C novyi-NT, could eradicate large established tumors.
引用
收藏
页码:15172 / 15177
页数:6
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