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
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
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DOI：
10.1007/s00262-020-02737-y
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发表时间：
2020-10-19
影响因子：
5.8
通讯作者：
Nagano, Hiroaki
中科院分区：
文献类型：
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作者：
Matsui, Hiroto Matsui;Hazama, Shoichi;Nagano, Hiroaki
简介 肝细胞癌 (HCC) 的蛋白质组学分析表明，热休克蛋白 70 (HSP70) 是 HCC 的癌症抗原蛋白之一。此外，我们通过免疫组化染色证实HSP70在HCC中高表达。基于这些结果，我们开发了一种HSP70 mRNA转染的树突状细胞（DC）疗法，用于治疗不可切除或复发性HCC，并已成功完成I期试验。因此，我们旨在通过开展 I/II 期随机对照临床试验来研究该疗法作为 HCC 根治性切除术后辅助治疗以预防复发的安全性和有效性。方法 对 II-IVa 期可切除 HCC 患者（n = 45）进行术前登记并随机分为两组（DC 组：31 例患者，对照组：14 例患者）。主要终点是无病生存期（DFS），次要终点是安全性和总生存期。 DC 疗法最初在手术后约 1 周进行，此后每 3-4 周进行两次。结果 DC 组未观察到免疫治疗特有的不良事件。 DC 组和对照组之间的 DFS 没有差异 (p = 0.666)。然而，在表达 HSP70 的 HCC 亚组中，DC 组的 DFS 往往更好（p = 0.090），DC 组的 OS 显着长于对照组（p = 0.003）。结论 HSP70 mRNA 转染的 DC 治疗作为辅助治疗是安全的。通过这种疗法，表达 HSP70 的 HCC 病例的预后有望得到改善。
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.