Background & objective: Alpha-fetoprotein (AFP) is a good candidate antigen for the immunotherapy of hepatocellular carcinoma (HCC). How to overcome the immune tolerance induced by autologous antigen is one of key points for inducing effective antitumor immune reaction. This research was to investigate the effect of human AFP-derived peptide-pulsed dendritic cells (hAFP-DCs) on immunity against mouse HCC.
Methods: Bone marrow-originated DCs were prepared routinely. The activity of hAFP-DC-stimulated cytotoxic T lymphocyte (CTL) against Hepa1-6 cells was examined by MTT assay. C57BL/6 mice were inoculated subcutaneously with 7 x 10(6) Hepa1-6 cells to develop hepatoma, and received intratumor injection of hAFP-DCs, DCs and PBS, respectively, twice a week. Tumor volume was evaluated and the survival of mice after inoculation was observed.
Results: We successfully prepared DCs from bone marrow of mice. The cytotoxic activity of CTLs stimulated by hAFP-DCs and DCs showed stronger tendency than that of control, but without significance. The mean tumor volume at 31 days after inoculation with Hepa1-6 cells was (195.04+/-155.22) mm3 in hAFP-DCs group, (360.65+/-209.02) mm3 in DCs group and (756.19+/-503.24) mm3 in PBS group. The differences among these three groups were significant (P < 0.001). The survival rate of mice at 40 days after inoculation was 100% in hAFP-DCs group, 90% in DCs group and 50% in PBS group (P=0.008).
Conclusion: Human AFP-derived peptide-pulsed DCs can efficiently enhance immunity against HCC in mice.