In Vivo Inhibitory Effect of Dendritic Cells with AFP cDNA Fragment (AFP/DC Vaccine) on Growth of Hepatocarcinoma Xenografts in BALB/C Mice
2007
[Objective] To discuss the in vitro immunological activity of dendritic cells (DCs) presenting alpha fetoprotein 1 (AFP1) with signal peptide or AFP2 without signal peptide, and their inhibitory effects on growth of hepatocarcinoma xenografts in BALB/c mice. [Methods] Eukaryotic expressing vectors pcDNA3.1(+) carrying AFP1 cDNA with signal peptide and AFP2 cDNA without signal peptide were constructed and transfected into DCs of BALB/c mice to prepare DC vaccines (AFP1/DC and AFP/DC). Spleen lymphocytes of BALB/c mice were cultured with these DC vaccines. The abilities of AFP1/DCs and AFP2/DCs to stimulate the proliferation of T lymphocytes in BALB/c mice and to induce specific killing effect of cytotoxic T lymphocytes (CTL) were observed, their therapeutic effects on subcutaneous xenografts in Balb/c mice were also observed. [Results] AFP2/DCs obviously enhanced the expression of IFN-γ, stimulated proliferation of T lymphocytes, and improved CTL activity. AFP1/DCs and AFP2/DCs remarkably inhibited the growth of hepatocarcinoma xenografts. Two weeks after treatment, the tumor volume was significantly smaller in AFP2/DCs group than in AFP/DCs group and empty plasmid control group [(726.7±290.2) mm^3 vs. (1486.2±457.2) mm^3 and (2137.2±547.2) mm^3, P<0.05]; the inhibitory rate of tumor growth was significantly lower in AFP2/DCs group and AFP1/DCs group than in empty plasmid control group (75.2% and 36.7% vs. 0%, P<0.05); the survival time of mice was significantly longer in AFP2/DCs group and AFP1/DCs group than in empty plasmid control group [(54.4±4.2) days and (40.2±4.8) days vs. (30.6±6.2) days, P<0.05]. [Conclusion] AFP2/DC and AFP1/DC vaccines can inhibit the growth of hepatocarcinoma xenografts in BALB/c mice through inducing efficient and specific immune response against hepatocarcinoma cells.
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