An attenuated Salmonella oral DNA vaccine prevents the growth of hepatocellular carcinoma and colon cancer that express alpha-fetoprotein.
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 alpha-fetoprotein (AFP) gene against a cancer line CT26-murine alpha-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.
Chou
C-K
CK
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Hung
J-Y
JY
Liu
J-C
JC
Chen
C-T
CT
Hung
M-C
MC
D000284:Administration, Oral; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000517:prevention & control*; D002460:Cell Line; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000517:prevention & control; D003602:Cytotoxicity, Immunologic; D005798:Genes, Bacterial; D006801:Humans; D007108:Immune Tolerance; D008113:Liver Neoplasms / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009876:Operon; D010957:Plasmids; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000276:immunology
D000951:Antigens, Neoplasm; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D000509:alpha-Fetoproteins