Therapeutic efficacy of dendritic cell vaccine combined with programmed death 1 inhibitor for hepatocellular carcinoma

Abstract

Background and aim: Hepatocellular carcinoma (HCC) remains a serious cause of cancer-related deaths worldwide. Developing new therapeutic strategies is urgently needed to improve the outcomes of HCC patients. Dendritic cell (DC)-based vaccines and programmed death 1 (PD-1) immune checkpoint inhibitors have been regarded as potential immunotherapeutics for HCC. However, the therapeutic efficacy of combining these two treatments for HCC remains to be evaluated.

Methods: In this study, DCs were derived from mouse bone marrow and pulsed with mouse HCC cell lysates to generate a DC vaccine. A monoclonal antibody that blocks the interaction of mouse PD-1 with its ligands was used as a PD-1 inhibitor. An orthotopic HCC mouse model was established to assess the effect of a DC vaccine in combination with a PD-1 inhibitor on overall survival and tumor volume.

Results: Compared with the untreated control, single treatment with a DC vaccine or PD-1 inhibitor prolonged the overall survival and reduced the tumor volume of HCC mice. Further, compared with the single treatment with the DC vaccine or the PD-1 inhibitor, a combination treatment using both agents elicited a higher cytotoxicity of T cells against HCC cells and resulted in a better overall survival, smaller tumor volume, and greater tumor cell apoptosis in HCC mice.

Conclusions: Our results suggest that a combination treatment with DC vaccine and PD-1 inhibitor may be a promising therapeutic strategy for HCC.

Keywords: combination treatment; dendritic cells; hepatocellular carcinoma; immune checkpoint inhibitor; programmed death 1.