Charneau Jimmy, Suzuki Toshihiro, Shimomura Manami, Fujinami Norihiro, Nakatsura Tetsuya
Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa City, Japan.
Department of Pharmacology, School of Medicine, Teikyo University, Tokyo, Japan.
J Hepatocell Carcinoma. 2021 Sep 2;8:1035-1054. doi: 10.2147/JHC.S291558. eCollection 2021.
Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. After surgery, up to 70% of patients experience relapses. The current first-line therapy for advanced cases of hepatocellular carcinoma (HCC) comprises sorafenib and lenvatinib administered as single-drug therapies. Regorafenib, cabozantinib, and ramucirumab are administered as second-line therapies. Recently, it has been reported that using the immune checkpoint inhibitors atezolizumab (anti-PDL1 antibody) and bevacizumab (anti-VEGF antibody) leads to longer overall survival of unresectable cases, when compared with the use of sorafenib. The role of cancer immunity against HCC has attracted the attention of clinicians. In this review, we describe our phase I/II clinical trials of peptide vaccines targeting GPC3 in HCC and discuss the potential of peptide vaccines targeting common cancer antigens that are highly expressed in HCC, such as WT-I, AFP, ROBO1, and FOXM1. Further, we introduce recent cancer vaccines targeting neoantigens, which have attracted attention in recent times, as well as present our preclinical studies, the results of which might aid to initiate a neoantigen vaccine clinical trial, which would be the first of its kind in Japan.
原发性肝癌是全球第六大常见诊断癌症，也是癌症相关死亡的第三大主要原因。手术后，高达70%的患者会复发。目前，肝细胞癌（HCC）晚期病例的一线治疗包括索拉非尼和乐伐替尼单药治疗。瑞戈非尼、卡博替尼和雷莫西尤单抗用作二线治疗。最近有报道称，与使用索拉非尼相比，使用免疫检查点抑制剂阿替利珠单抗（抗PDL1抗体）和贝伐单抗（抗VEGF抗体）可使不可切除病例的总生存期延长。癌症免疫对HCC的作用已引起临床医生的关注。在本综述中，我们描述了针对HCC中GPC3的肽疫苗的I/II期临床试验，并讨论了针对在HCC中高表达的常见癌症抗原（如WT-1、甲胎蛋白、ROBO1和FOXM1）的肽疫苗的潜力。此外，我们介绍了最近受到关注的针对新抗原的癌症疫苗，并展示了我们的临床前研究结果，这些结果可能有助于启动日本首个此类新抗原疫苗的临床试验。
