[DNA vaccine encoding alpha-fetoprotein with fused ornithine decarboxylase degradation signal significantly suppresses hepatocellular carcinoma growth in mice].
Hepatocellular carcinoma (HCC) is among the most frequent malignancies in humans. HCC therapy is not efficient and the usual outcome is poor. In this regard, novel approaches to treat and prevent HCC are urgently needed. The Alpha-fetoprotein (AFP) is a serological marker of HCC. Recently it has been shown, that the DNA vaccines expressing AFP are capable in generating immune response against AFP. However, both, the immunization procedures and DNA vaccines used before were complex and not always very effective. We have shown that DNA vaccine encoding HIV-1 reverse transcriptase (RT) with fused ornithine decarboxylase (ODC) degradation signal induced a strong Th-1 immune response against RT in mice. Using this approach we designed a set of novel DNA vaccines bearing AFP and ODC degradation signal. Results obtained on transfected cells demonstrated efficient expression and fast proteasomal degradation of the recombinant AFP. The anti-tumor immune response stimulation was shown in immunized animals and most importantly a notable retardation of tumor growth was observed as a result of protective vaccination.
A V
AV
Morozov
V A
VA
Morozov
T M
TM
Astakhova
A V
AV
Timofeev
V L
VL
Karpov
D056704:Adaptive Immunity; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D057809:HEK293 Cells; D054303:HIV Reverse Transcriptase / Q000235:genetics; D006801:Humans; D007114:Immunization; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000276:immunology*; D010957:Plasmids; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D000509:alpha-Fetoproteins / Q000235:genetics / Q000276:immunology*
D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D000509:alpha-Fetoproteins; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D046988:Proteasome Endopeptidase Complex; D009955:Ornithine Decarboxylase