Dendritic cells pulsed with Hsp70 and HBxAg induce specific antitumor immune responses in hepatitis B virus-associated hepatocellular carcinoma

Abstract

Previous studies have drawn attention to dendritic cell (DC) vaccines; particularly the application of the tumor-associated antigen-targeted DC vaccine. The present study analyzed DCs derived from a normal individual and pulsed the cells with heat shock protein 70 peptide (Hsp70) and/or hepatitis B virus x antigen (HBxAg), a hepatocellular carcinoma (HCC)-associated antigen. It was then investigated whether this method of vaccination induced strong therapeutic antitumor immunity. The results revealed that the Hsp70/HBxAg complex-activated phenotype improves the functional maturation of DCs compared with using Hsp70 or HBxAg alone. Compared with either Hsp70 or HBxAg alone, matured DCs pulsed with the Hsp70/HBxAg complex stimulated a high level of autologous T-cell proliferation and induced HCC-specific cytotoxic T lymphocytes, which specifically killed HCC cells through a major histocompatibility complex class I mechanism. These results indicated that a vaccination therapy using DCs co-pulsed with the Hsp70/HBxAg complex is an effective strategy for immunotherapy and may offer a useful approach to protect against HCC.