Journal
MOLECULAR THERAPY
Volume 18, Issue 3, Pages 635-642Publisher
CELL PRESS
DOI: 10.1038/mt.2009.295
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Funding
- Ministry of Education, Science and Technology [2008-04131, 2009-0091729]
- National R&D Program for Cancer Control [0620330-1]
- Ministry of Health & Welfare, Republic of Korea
- Ministry of Commerce, Industry and Energy (MOCIE) [RTI05-01-01]
- MOST, Republic of Korea [M20702010003-07N0201-00300]
- Korean government [2007-04213]
- Korea Evaluation Institute of Industrial Technology (KEIT) [B0008558] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Korea Health Promotion Institute [0620330] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2007-2004213, 2007-2000329, 2007-2004219, 2008-04131, 2009-0091729] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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