Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatocellular carcinoma: a phase I/II prospective randomized controlled clinical trial.

INTRODUCTION: A proteomic analysis of hepatocellular carcinoma (HCC) has revealed that Heat Shock Protein 70 (HSP70) is among the cancer antigen proteins of HCC. Moreover, we confirmed that HSP70 was highly expressed in HCC by immunohistochemical staining. Based on these results, we developed an HSP70 mRNA-transfected dendritic cell (DC) therapy for treating unresectable or recurrent HCC, and the phase I trial was completed successfully. Thus, we aimed to investigate the safety and efficacy of this therapy as a postoperative adjuvant treatment after curative resection for HCC to prevent recurrence by conducting a phase I/II randomized controlled clinical trial. METHODS: Patients (n = 45) with resectable HCC of stages II-IVa were registered and randomly assigned into two groups (DC group: 31 patients, control group: 14 patients) before surgery. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were safety and overall survival. The DC therapy was initially administered at approximately 1 week after surgery, and twice every 3-4 weeks thereafter. RESULTS: No adverse events specific to the immunotherapy were observed in the DC group. There was no difference in DFS between the DC and control groups (p = 0.666). However, in the subgroup with HSP70-expressing HCC, DFS of the DC group tended to be better (p = 0.090) and OS of the DC group was significantly longer (p = 0.003) than those of the control group. CONCLUSION: The HSP70 mRNA-transfected DC therapy was performed safely as an adjuvant therapy. The prognosis of HSP70-expressing HCC cases could be expected to improve with this therapy.