Tumor-targeting prodrug-activating bacteria for cancer therapy

C. M. Cheng, Y. L. Lu, K. H. Chuang, W. C. Hung, J. Shiea, Y. C. Su, C. H. Kao, B. M. Chen, S. Roffler, T. L. Cheng

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Increasing the specificity of chemotherapy may improve the efficacy of cancer treatment. Toward this aim, we developed a strain of bacteria to express enzymes for selective prodrug activation and non-invasive imaging in tumors. β-glucuronidase and the luxCDABE gene cluster were expressed in the DH5α strain of Escherichia coli to generate DH5α-lux/βG. These bacteria emitted light for imaging and hydrolyzed the glucuronide prodrug 9ACG to the topoisomerase I inhibitor 9-aminocamptothecin (9AC). By optical imaging, colony-forming units (CFUs) and staining for βG activity, we found that DH5α-lux/βG preferentially localized and replicated within CL1-5 human lung tumors in mice. The intensity of luminescence, CFU and βG activity increased with time, indicating bacterial replication occurred in tumors. In comparison with DH5α-lux/βG, 9AC or 9ACG treatment, combined systemic administration of DH5α-lux/βG followed by 9ACG prodrug treatment significantly (P

Original languageEnglish
Pages (from-to)393-401
Number of pages9
JournalCancer Gene Therapy
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes

Fingerprint

9-aminocamptothecin
Prodrugs
Bacteria
Neoplasms
Stem Cells
Topoisomerase I Inhibitors
Optical Imaging
Glucuronidase
Glucuronides
Therapeutics
Multigene Family
Luminescence
Staining and Labeling
Escherichia coli
Light
Drug Therapy
Lung
Enzymes

Keywords

  • β-glucuronidase
  • Glucuronide prodrug
  • Luminescence
  • Non-invasive imaging
  • Optical imaging
  • Prodrug-activating bacteria

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Cheng, C. M., Lu, Y. L., Chuang, K. H., Hung, W. C., Shiea, J., Su, Y. C., ... Cheng, T. L. (2008). Tumor-targeting prodrug-activating bacteria for cancer therapy. Cancer Gene Therapy, 15(6), 393-401. https://doi.org/10.1038/cgt.2008.10

Tumor-targeting prodrug-activating bacteria for cancer therapy. / Cheng, C. M.; Lu, Y. L.; Chuang, K. H.; Hung, W. C.; Shiea, J.; Su, Y. C.; Kao, C. H.; Chen, B. M.; Roffler, S.; Cheng, T. L.

In: Cancer Gene Therapy, Vol. 15, No. 6, 06.2008, p. 393-401.

Research output: Contribution to journalArticle

Cheng, CM, Lu, YL, Chuang, KH, Hung, WC, Shiea, J, Su, YC, Kao, CH, Chen, BM, Roffler, S & Cheng, TL 2008, 'Tumor-targeting prodrug-activating bacteria for cancer therapy', Cancer Gene Therapy, vol. 15, no. 6, pp. 393-401. https://doi.org/10.1038/cgt.2008.10
Cheng, C. M. ; Lu, Y. L. ; Chuang, K. H. ; Hung, W. C. ; Shiea, J. ; Su, Y. C. ; Kao, C. H. ; Chen, B. M. ; Roffler, S. ; Cheng, T. L. / Tumor-targeting prodrug-activating bacteria for cancer therapy. In: Cancer Gene Therapy. 2008 ; Vol. 15, No. 6. pp. 393-401.
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