WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies

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.

胸腺瘤上皮肿瘤是罕见的恶性肿瘤，对于晚期患者尚未确定最佳治疗方案。对既往治疗耐药或不耐受的晚期胸腺瘤上皮肿瘤患者符合本研究的入组条件。患者每周一次通过皮内注射接受由Montanide ISA51佐剂乳化的9聚体野生型WT1衍生肽作为单一疗法。在3个月的方案治疗后，治疗大多以2 - 4周的间隔持续进行，直至疾病进展或出现无法耐受的不良事件。在入组的15名患者中，11名患有胸腺癌（TC），4名患有侵袭性胸腺瘤（IT）。从诊断到开始治疗的中位时间，TC患者为13.3个月，IT患者为65.5个月。没有患者达到完全缓解或部分缓解。在8名可评估的TC患者中，6名（75.0%）病情稳定（SD），2名病情进展（PD）。在4名可评估的IT患者中，3名（75.0%）病情稳定，1名（25.0%）病情进展。TC和IT患者单一疗法治疗的中位时间分别为133天和683天。在3个月的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，两名IT患者出现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。一名合并血管性血友病的TC患者发生小脑出血。在大多数患者中观察到WT1特异性免疫反应的诱导。WT1肽疫苗免疫疗法可能对胸腺瘤恶性肿瘤具有抗肿瘤潜力。有何新进展？由于WT1蛋白在多种癌症中过度表达，它是癌症免疫疗法的一个有前景的靶点。在这项针对晚期胸腺瘤的II期临床试验中，作者测试了用WT1肽为患者接种疫苗的疗效。虽然这并未使肿瘤缩小，但75%的患者在数月内病情保持稳定。由于胸腺瘤往往直到晚期才被发现，WT1免疫疗法可能为这些难治性癌症提供一种有用的辅助方法。