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An attenuated Salmonella oral DNA vaccine prevents the growth of hepatocellular carcinoma and colon cancer that express α-fetoprotein

Cancer Gene Therapy volume 13, pages 746–752 (2006)Cite this article

Abstract

Antitumor vaccination therapies using attenuated Salmonella typhimurium carrying plasmid DNA encoding tumor-associated antigens are currently under preclinical development. In the present study, we first established a useful method to facilitate in vivo monitoring of attenuated S. typhimurium uptake using a bioluminescent lux gene operon plasmid. Following transformation with the lux gene operon construct, mice were fed with various amounts of attenuated S. typhimurium-lux to monitor in vivo clearance over a period of 24 h. We found that the ingested attenuated S. typhimurium-lux cells were almost cleared out 9 h postfeeding, as judged by a significant decrease in bioluminescence. We further examined the therapeutic efficacy of vaccination using attenuated S. typhimurium carrying the mouse α-fetoprotein (AFP) gene against a cancer line CT26-murine α-feto protein (mAFP) that stably expresses AFP and mouse hepatocellular carcinoma (HCC) Hepa1-6. Attenuated S. typhimurium oral DNA vaccine was found to promote protective immunity against both CT26-mAFP and Hepa1-6 tumor cells growth. The oral DNA vaccine significantly increased the life span of tumor-challenged mice in both tumor models. Together, these results suggest that vaccination with the attenuated S. typhimurium oral DNA vaccine that carries the AFP gene could be a promising strategy to prevent HCC development.

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Acknowledgements

We thank Dr Hui-Wen Lo at Department of Molecular and Cellular Oncology and Sandra Young at Department of Scientific Publication at the University of Texas MD Anderson Cancer Center for editing the manuscript. This work was supported by Grants from SPORE in Ovarian Cancer P50CA83639, SPORE in Pancreatic Cancer P20CA101936 and Kadoorie Charitable Foundation (to M-C Hung). J-YH was partially supported by the Kaohsiung Medical University Hospital, Taiwan.

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Author notes

  1. C-K Chou and J-Y Hung: Visiting Scientist from the Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China.

  2. J-Y Hung: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    C-K Chou, J-Y Hung, J-C Liu, C-T Chen & M-C Hung

  2. Cancer Biology Program, Graduate School of Biomedical Science, The University of Texas, Health Science Center at Houston, Houston, TX, USA

    C-K Chou & M-C Hung

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  1. C-K Chou
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  2. J-Y Hung
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Correspondence to M-C Hung.

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Chou, CK., Hung, JY., Liu, JC. et al. An attenuated Salmonella oral DNA vaccine prevents the growth of hepatocellular carcinoma and colon cancer that express α-fetoprotein. Cancer Gene Ther 13, 746–752 (2006). https://doi.org/10.1038/sj.cgt.7700927

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