WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies
WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies
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DOI：
10.1002/ijc.31253
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发表时间：
2018-06-01
影响因子：
6.4
通讯作者：
Sugiyama, Haruo
中科院分区：
文献类型：
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作者：
Oji, Yusuke;Inoue, Masayoshi;Sugiyama, Haruo
胸腺上皮性肿瘤是一种罕见的恶性肿瘤，目前还没有最佳的治疗方案。对既往治疗耐药或不耐受的晚期胸腺上皮肿瘤患者有资格参加本研究。患者每周一次通过皮内给药接受用Montanide ISA 51佐剂乳化的9 mer-WT 1衍生肽作为单一疗法。在3个月的方案治疗后，大多数情况下以2-4周的间隔继续治疗，直至疾病进展或发生不可耐受的不良事件。在入选的15例患者中，11例患有胸腺癌（TC），4例患有浸润性胸腺瘤（IT）。TC和IT从诊断到开始治疗的中位时间分别为13.3和65.5个月。没有患者达到完全或部分缓解。在8例可评价的TC患者中，6例（75.0%）疾病稳定（SD），2例疾病进展（PD）。在4例可评价IT患者中，3例（75.0%）为SD，1例（25.0%）为PD。TC和IT患者单药治疗的中位时间分别为133天和683天。3个月方案治疗期间未发生严重不良事件。作为长期应答者的不良事件，2例IT患者发生胸腺瘤相关自身免疫并发症、纯红细胞再生障碍性贫血和重症肌无力。小脑出血发生在TC患者并发血管性血友病。在大多数患者中观察到WT 1特异性免疫应答的诱导。WT 1肽疫苗免疫疗法可能对胸腺恶性肿瘤具有抗肿瘤潜力。因为它在许多类型的癌症中过表达，WT 1蛋白是癌症免疫治疗的一个有前途的靶点。在这个晚期胸腺癌的II期临床试验中，作者测试了用WT 1肽接种患者的有效性。虽然这并没有缩小肿瘤，但75%的患者在几个月内保持稳定的疾病。由于胸腺肿瘤通常在晚期才被发现，因此WT 1免疫疗法可能为这些困难的癌症提供有用的辅助方法。
Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer-WT1-derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3-month-protocol treatment, the treatment was continued mostly at intervals of 2-4 weeks until disease progression or intolerable adverse events occurred. Of the 15 patients enrolled, 11 had thymic carcinoma (TC) and 4 had invasive thymoma (IT). Median period from diagnosis to the start of treatment was 13.3 and 65.5 months for TC and IT, respectively. No patients achieved a complete or partial response. Of the 8 evaluable TC patients, 6 (75.0%) had stable disease (SD) and 2 had progressive disease (PD). Of the 4 evaluable IT patients, 3 (75.0%) had SD and 1 (25.0%) had PD. Median period of monotherapy treatment was 133 and 683 days in TC and IT patients, respectively. No severe adverse events occurred during the 3-month-protocol treatment. As adverse events in long responders, thymoma-related autoimmune complications, pure red cell aplasia and myasthenia gravis occurred in two IT patients. Cerebellar hemorrhage developed in a TC patient complicated with Von Willebrand disease. Induction of WT1-specific immune responses was observed in the majority of the patients. WT1 peptide vaccine immunotherapy may have antitumor potential against thymic malignancies.What's new? Because it is overexpressed in many types of cancer, the protein WT1 is a promising target for cancer immunotherapy. In this phase II clinical trial in advanced thymic cancers, the authors tested the efficacy of vaccinating patients with a WT1 peptide. While this did not shrink the tumors, 75% of patients maintained stable disease over several months. Because thymic tumors often go undetected until an advanced stage, WT1 immunotherapy may offer a useful adjunct approach in these difficult cancers.