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.
Agrawal
Nishant
N
Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Bettegowda
Chetan
C
Cheong
Ian
I
Geschwind
Jean-Francois
JF
Drake
Charles G
CG
Hipkiss
Edward L
EL
Tatsumi
Mitsuaki
M
Dang
Long H
LH
Diaz
Luis A
LA
Pomper
Martin
M
Abusedera
Mohammad
M
Wahl
Richard L
RL
Kinzler
Kenneth W
KW
Zhou
Shibin
S
Huso
David L
DL
Vogelstein
Bert
B
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