Oji Yusuke, Kagawa Naoki, Arita Hideyuki, Naka Norifumi, Hamada Ken-Ichiro, Outani Hidetatsu, Shintani Yasushi, Takeda Yoshito, Morii Eiichi, Shimazu Kenzo, Suzuki Motoyuki, Nishida Sumiyuki, Nakata Jun, Tsuboi Akihiro, Iwai Miki, Hayashi Sae, Imanishi Rin, Ikejima Sayaka, Kanegae Mizuki, Iwamoto Masahiro, Ikeda Mayu, Yagi Kento, Shimokado Haruka, Nakajima Hiroko, Hasegawa Kana, Morimoto Soyoko, Fujiki Fumihiro, Nagahara Akira, Tanemura Atsushi, Ueda Yutaka, Mizushima Tsunekazu, Ohmi Masato, Ishida Takayuki, Fujimoto Manabu, Nonomura Norio, Kimura Tadashi, Inohara Hidenori, Okada Seiji, Kishima Haruhiko, Hosen Naoki, Kumanogoh Atsushi, Oka Yoshihiro, Sugiyama Haruo
Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Cancers (Basel). 2023 Jan 6;15(2):393. doi: 10.3390/cancers15020393.
No standard treatment has been established for most rare cancers. Here, we report a clinical trial of a biweekly WT1 tri-peptide-based vaccine for recurrent or advanced rare cancers. Due to the insufficient number of patients available for a traditional clinical trial, the trial was designed for rare cancers expressing shared target molecule WT1. The recruitment criteria included WT1-expressing tumors as well as HLA-A*24:02 or 02:01. The primary endpoints were immunoglobulin G (IgG) antibody (Ab) production against the WT1-235 cytotoxic T lymphocyte (CTL) epitope and delayed-type hypersensitivity (DTH) skin reactions to targeted WT1 CTL epitopes. The secondary endpoints were safety and clinical efficacy. Forty-five patients received WT1 Trio, and 25 (55.6%) completed the 3-month protocol treatment. WT1-235 IgG Ab was positive in 88.0% of patients treated with WT1 Trio at 3 months, significantly higher than 62.5% of the weekly WT1-235 CTL peptide vaccine. The DTH positivity rate in WT1 Trio was 62.9%, which was not significantly different from 60.7% in the WT1-235 CTL peptide vaccine. The WT1 Trio safety was confirmed without severe treatment-related adverse events, except grade 3 myasthenia gravis-like symptoms observed in a patient with thymic cancer. Fifteen (33.3%) patients achieved stable disease after 3 months of treatment. In conclusion, the biweekly WT1 Trio vaccine containing the WT1-332 helper T lymphocyte peptide induced more robust immune responses targeting WT1 than the weekly WT1-235 CTL peptide vaccine. Therefore, WT1-targeted immunotherapy may be a potential therapeutic strategy for rare cancers.
大多数罕见癌症尚未确立标准治疗方法。在此，我们报告了一项针对复发或晚期罕见癌症的基于WT1三肽的双周疫苗临床试验。由于传统临床试验可用患者数量不足，该试验针对表达共同靶分子WT1的罕见癌症进行设计。招募标准包括表达WT1的肿瘤以及HLA - A*24:02或02:01。主要终点是针对WT1 - 235细胞毒性T淋巴细胞（CTL）表位的免疫球蛋白G（IgG）抗体产生以及对靶向WT1 CTL表位的迟发型超敏反应（DTH）皮肤反应。次要终点是安全性和临床疗效。45例患者接受了WT1三肽疫苗治疗，25例（55.6%）完成了3个月的方案治疗。在3个月时，接受WT1三肽疫苗治疗的患者中88.0%的WT1 - 235 IgG抗体呈阳性，显著高于每周一次的WT1 - 235 CTL肽疫苗的62.5%。WT1三肽疫苗的DTH阳性率为62.9%，与WT1 - 235 CTL肽疫苗的60.7%无显著差异。WT1三肽疫苗的安全性得到证实，除了1例胸腺癌患者出现3级重症肌无力样症状外，未发生严重的治疗相关不良事件。15例（33.3%）患者在治疗3个月后病情稳定。总之，含有WT1 - 332辅助性T淋巴细胞肽的双周WT1三肽疫苗比每周一次的WT1 - 235 CTL肽疫苗诱导出更强的针对WT1的免疫反应。因此，针对WT1的免疫疗法可能是罕见癌症的一种潜在治疗策略。
