title: Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
authors.forename: Long H
authors.initials: LH
authors.lastname: Dang
authors.forename: Ross
authors.initials: R
authors.lastname: Abrams
authors.forename: David L
authors.initials: DL
authors.lastname: Huso
authors.forename: Larry
authors.initials: L
authors.lastname: Dillehay
authors.forename: Ian
authors.initials: I
authors.lastname: Cheong
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
authors.forename: Scott
authors.initials: S
authors.lastname: Borzillary
authors.forename: J Michael
authors.initials: JM
authors.lastname: McCaffery
authors.forename: E Latice
authors.initials: EL
authors.lastname: Watson
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
authors.forename: Fred
authors.initials: F
authors.lastname: Bunz
authors.forename: Kwamena
authors.initials: K
authors.lastname: Baidoo
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Shibin
authors.initials: S
authors.lastname: Zhou
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D002588:Cesium Radioisotopes