Inhibition of tumor growth and metastasis by a combination of Escherichia coli-mediated cytolytic therapy and radiotherapy.
We have reported that Escherichia coli K-12 colonizes hypoxic and necrotic tumor regions after intravenous injection into tumor-bearing mice. In this study, we established a novel strategy for cancer therapy using engineered bacteria to enhance the therapeutic effects of radiation. E. coli strain K-12 was engineered to produce cytolysin A (ClyA), and its effects on tumor growth in primary and metastatic tumor models were evaluated. A single treatment with E. coli-expressing ClyA significantly decreased tumor growth rates initially (9 days after treatment); however, the tumors tended to grow thereafter. With only radiotherapy (RT; 21 Gy), the tumor growth rates were retarded, but not the tumor sizes. A combination of therapy with E. coli-expressing ClyA and radiation [a total of 5 x 10(7) colony-forming units (CFU) and 21 Gy] resulted in significant tumor shrinkage and even complete disappearance of tumors in mice with tumors derived from murine CT26 colon cancer. Furthermore, treatment with E. coli-expressing ClyA markedly suppressed metastatic tumor growth and prolonged the survival time in mice. The results described here indicate that therapy with engineered E. coli could significantly improve the results of RT, and could exert a striking inhibitory effect on the development of lung metastasis.
Jiang
Sheng-Nan
SN
Laboratory of In Vivo Molecular Imaging, Chonnam National University Medical School, Gwangju, Republic of Korea.
Phan
Thuy X
TX
Nam
Taek-Keun
TK
Nguyen
Vu H
VH
Kim
Hyung-Seok
HS
Bom
Hee-Seung
HS
Choy
Hyon E
HE
Hong
Yeongjin
Y
Min
Jung-Joon
JJ
D000818:Animals; D045744:Cell Line, Tumor; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004926:Escherichia coli / Q000378:metabolism*; D000860:Hypoxia; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000628:therapy*; D054353:Perforin / Q000378:metabolism; D011878:Radiotherapy / Q000379:methods*; D013234:Stem Cells
D054353:Perforin