Immune Reactions against Hepatitis B Viral Antigens Lead to the Rejection of Hepatocellular Carcinoma in BALB/c Mice

Human hepatitis B virus (HBV) is closely associated with hepatocellular carcinoma. However, the mechanism of carcinogenesis and the immune responses to HBV infection and hepatocellular carcinoma are not clearly understood. Recently, we established BALB/c mouse liver (ML) cell lines and demonstrated that transfection of ML cell lines with HBV dimer DNA resulted in the expression of HBV antigens (1). The HBV-transfected ML cells and the parental ML cells showed similar tumorigenicity in nude mice. However, the HBV-transfected cells had much lower tumorigenicity in BALB/c mice. Similar results were also obtained in two cloned ML cell lines, ML-1.1 and ML-1.2, transfected with plasmid DNA containing HBs, HBc, or HBx gene. Furthermore, adoptive transfer of spleen cells from BALB/c mice immunized with HBsAg- or HBcAg-expressing ML-1.1 cells caused regression of tumor cells expressing the corresponding antigens in nude mice. In addition, transfer of spleen cells from BALB/c mice immunized with purified HBsAg or HBcAg also caused tumor regression. These results demonstrate that HBsAg and HBcAg can induce immunity which leads to the rejection of hepatocellular carcinoma in vivo.