Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain.
Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, SalmonellaTyphimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do.
Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
Bin
B
Yu
Mei
M
Yang
Lei
L
Shi
Yandan
Y
Yao
Qinqin
Q
Jiang
Xuefei
X
Li
Lei-Han
LH
Tang
Bo-Jian
BJ
Zheng
Kwok-Yung
KY
Yuen
David K
DK
Smith
Erwei
E
Song
Jian-Dong
JD
Huang
D000818:Animals; D001421:Bacteria, Anaerobic / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D001428:Bacterial Vaccines / Q000494:pharmacology; D001691:Biological Therapy / Q000379:methods; D001943:Breast Neoplasms / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D005818:Genetic Engineering / Q000379:methods; D054884:Host-Pathogen Interactions; D006801:Humans; D000860:Hypoxia; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000382:microbiology* / Q000473:pathology / Q000628:therapy; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D047368:Tumor Burden / Q000187:drug effects; D014774:Virulence / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D001428:Bacterial Vaccines; C465023:VNP 20009