Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatoc
- PDF / 1,293,601 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 25 Downloads / 214 Views
ORIGINAL ARTICLE
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 Hiroto Matsui Matsui1 · Shoichi Hazama1,2 · Masao Nakajima1 · Ming Xu1 · Satoshi Matsukuma1 · Yukio Tokumitsu1 · Yoshitaro Shindo1 · Shinobu Tomochika1 · Shin Yoshida1 · Michihisa Iida1 · Nobuaki Suzuki1 · Shigeru Takeda1 · Shigefumi Yoshino1,3 · Tomio Ueno4 · Masaaki Oka5 · Hiroaki Nagano1 Received: 9 April 2020 / Accepted: 2 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords HSP70 · Dendritic cell therapy · Immunotherapy · Hepatocellular carcinoma
Introduction
Immunotherapy targeting HSP70 as a tumor-associated antigen (TSA) using mRNA-transfected DC was safe and effective for curatively resected HSP70-expressing HCC. This study revealed HSP70 could be a TSA for the immunotherapy against HCC. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02737-y) contains supplementary material, which is available to authorized users. * Hiroaki Nagano hnagano@yamaguchi‑u.ac.jp Extended author information available on the last page of the article
The recurrence rate of hepatocellular carcinoma (HCC) is still high even after its curative resection; thus, an adjuvant therapy for preventing the recurr
Data Loading...
