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Tumor-targeting prodrug-activating bacteria for cancer therapy

Cancer Gene Therapy volume 15, pages 393–401 (2008)Cite this article

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<0.005) delayed the growth of CL1-5 tumors. Our results demonstrate that prodrug-activating bacteria may be useful for selective cancer chemotherapy.

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Acknowledgements

This work was supported by the National Research Program for Genomic Medicine (NRPGM), National Science Council, Taipei, Taiwan (NSC95-3112-B-037-001) and the National Health Research Institutes (NHRI-EX96-9420BI, NHRI-EX96-9624SI). The National Sun Yat-Sen University-Kaohsiung Medical University joint research center is also gratefully acknowledged.

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Author notes

  1. C-M Cheng and Y-L Lu: These authors contributed equally to this work.

Authors and Affiliations

  1. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    C-M Cheng, K-H Chuang & C-H Kao

  2. Chia Nan University of Pharmacy and Science, Tainan, Taiwan

    Y-L Lu

  3. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

    W-C Hung

  4. National Sun Yat-Sen, University-Kaohsiung medical University Joint Research Center, Kaohsiung, Taiwan

    W-C Hung, J Shiea & T-L Cheng

  5. Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan

    J Shiea

  6. Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan

    Y-C Su & T-L Cheng

  7. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    B-M Chen & S Roffler

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  1. C-M Cheng
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Correspondence to S Roffler or T-L Cheng.

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Cheng, CM., Lu, YL., Chuang, KH. et al. Tumor-targeting prodrug-activating bacteria for cancer therapy. Cancer Gene Ther 15, 393–401 (2008). https://doi.org/10.1038/cgt.2008.10

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