Immunotherapy of hepatocellular carcinoma with a vaccine based on xenogeneic homologous alpha fetoprotein in mice.

alpha-Fetoprotein (AFP) is a diagnostic marker for the presence of hepatocellular carcinoma, and a potential target for immunotherapy. Unfortunately, the immunity to AFP is presumably difficult to elicit because of immune tolerance acquired during the development of immune system. In the present study, we used AFP as a model antigen to explore the feasibility of the immunotherapy of AFP-positive liver cancer by the breaking of immune tolerance against AFP in a cross-reaction between the xenogeneic homologues and self molecules. Recombinant rat AFP was prepared as a vaccine, and mouse AFP was prepared as a control. Immunized with rat AFP was effective at protective and therapeutic antitumor immunity in hepatocellular carcinoma model in mice. Both humoral and cellular immune responses may be responsible for the antitumor activity against AFP-positive tumor cells, and no marked side effects were observed in the immunized mice. Thus, our study may provide an effective vaccine strategy for the treatment of AFP-positive hepatocellular carcinoma, and may be of importance to further exploration of the breaking of immune tolerance to self molecules.