Dendritic cells fused with allogeneic hepatocellular carcinoma cell line compared with fused autologous tumor cells as hepatocellular carcinoma vaccines

Abstract

To investigate the specific antitumor responses against autologous hepatocellular carcinoma (HCC) cells of dendritic cells (DCs) fused with allogeneic HCC cell line, and evaluated the feasibility of BEL7402 as an alternative strategy to deliver shared HCC antigens to DCs. Previous studies demonstrated fusions of patient-derived DCs and autologous tumor cells could induce T-cell responses against autologous tumors. These fusion cells require patient-derived tumor cells, which are not, however, always available. Here, we report the fusing of autologous DCs with allogeneic HCC cell line to induced cytotoxic T-lymphocyte (CTL) response against autologous HCC cells compare with autologous tumor cells. These DC/ BEL7402 fusion cells co-expressed tumor-associated antigens and DC-derived costimulatory and major histocompatibility complex molecules. Both CD4+ and CD8 T+ cells were activated by the fusion cells as demonstrated by the proliferation of T-cells, the production of cytokines and the simultaneous induction of specific CTL responses. Significantly, CTL induced by dendritic cell/allogeneic BEL7402 fusion cells were able to kill autologous HCC cells by human leukocyte antigen-A2 restricted mechanisms. The results did not show significant difference between DC fusion with autologous hepatocellular carcinoma cells and DC fusion with allogeneic hepatocellular carcinoma cell line. The fusion of allogeneic HCC cell line and autologous DCs may have applications in antitumor immunotherapy through cross-priming against shared tumor antigens and may provide a platform for adoptive immunotherapy.