Bacteriolytic therapy can generate a potent immune response against experimental tumors.
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 approximately 30% 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.
Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Nishant
N
Agrawal
Chetan
C
Bettegowda
Ian
I
Cheong
Jean-Francois
JF
Geschwind
Charles G
CG
Drake
Edward L
EL
Hipkiss
Mitsuaki
M
Tatsumi
Long H
LH
Dang
Luis A
LA
Diaz
Martin
M
Pomper
Mohammad
M
Abusedera
Richard L
RL
Wahl
Kenneth W
KW
Kinzler
Shibin
S
Zhou
David L
DL
Huso
Bert
B
Vogelstein
D019264:Adoptive Transfer; D000818:Animals; D001433:Bacteriolysis; D045744:Cell Line, Tumor; D003013:Clostridium / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D013171:Spores, Bacterial / Q000276:immunology