Abstract: 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.

Keywords: common cancer antigen, cancer vaccine, glypican-3, neoantigen, personalized peptide vaccine


中文翻译：

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用于肝细胞癌的肽基疫苗：最新进展综述

摘要：原发性肝癌是全球第六大最常见的癌症，也是全球癌症相关死亡的第三大原因。手术后，高达 70% 的患者会复发。目前用于晚期肝细胞癌 (HCC) 病例的一线治疗包括索拉非尼和乐伐替尼作为单药治疗给药。瑞戈非尼、卡博替尼和雷莫芦单抗作为二线疗法给药。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 atezolizumab（抗 PDL1 抗体）和贝伐单抗（抗 VEGF 抗体）可延长不可切除病例的总生存期。癌症免疫对 HCC 的作用引起了临床医生的关注。在这次审查中，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 HCC 中高度表达的常见癌症抗原（如 WT-I、AFP、ROBO1 和 FOXM1）的肽疫苗的潜力。此外，我们还介绍了近期备受关注的针对新抗原的癌症疫苗，并介绍了我们的临床前研究，其结果可能有助于启动新抗原疫苗临床试验，这将在日本尚属首次.

关键词：常见癌抗原，癌症疫苗，glypican-3，新抗原，个性化多肽疫苗