Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria.
The low level of oxygenation within tumors is a major cause of radiation treatment failures. We theorized that anaerobic bacteria that can selectively destroy the hypoxic regions of tumors would enhance the effects of radiation. To test this hypothesis, we used spores of Clostridium novyi-NT to treat transplanted tumors in mice. The bacteria were found to markedly improve the efficacy of radiotherapy in several of the mouse models tested. Enhancement was noted with external beam radiation derived from a Cs-137 source, systemic radioimmunotherapy with an I-131-conjugated monoclonal antibody, and a previously undescribed form of experimental brachytherapy using plaques loaded with I-125 seeds. C. novyi-NT spores added little toxicity to the radiotherapeutic regimens, and the combination resulted in long-term remissions in a significant fraction of animals.
Bettegowda
Chetan
C
Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Dang
Long H
LH
Abrams
Ross
R
Huso
David L
DL
Dillehay
Larry
L
Cheong
Ian
I
Agrawal
Nishant
N
Borzillary
Scott
S
McCaffery
J Michael
JM
Watson
E Latice
EL
Lin
Kuo-Shyan
KS
Bunz
Fred
F
Baidoo
Kwamena
K
Pomper
Martin G
MG
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Zhou
Shibin
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001421:Bacteria, Anaerobic; D001918:Brachytherapy / Q000379:methods*; D002460:Cell Line; D045744:Cell Line, Tumor; D002588:Cesium Radioisotopes; D003013:Clostridium / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D000860:Hypoxia; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D016499:Radioimmunotherapy / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D002588:Cesium Radioisotopes