Wilms tumor 1 peptide vaccination combined with temozolomide against newly diagnosed glioblastoma: safety and impact on immunological response
Wilms tumor 1 peptide vaccination combined with temozolomide against newly diagnosed glioblastoma: safety and impact on immunological response
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DOI：
10.1007/s00262-015-1674-8
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发表时间：
2015-06-01
影响因子：
5.8
通讯作者：
Sugiyama, Haruo
中科院分区：
文献类型：
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作者：
Hashimoto, Naoya;Tsuboi, Akihiro;Sugiyama, Haruo
为了研究Wilms肿瘤1肽疫苗联合替莫唑胺治疗胶质母细胞瘤的安全性，设计了I期临床试验。7例组织学诊断为胶质母细胞瘤的患者接受了同步放疗和替莫唑胺治疗。患者在联合并行放射性/替莫唑胺治疗结束后1周首次接受肾母细胞瘤1肽疫苗接种，并继续每周一次给药，持续7周。开始替莫唑胺维持治疗并进行长达24个周期，安全性观察期包括从首次给予替莫唑胺维持治疗起6周。所有患者在观察期间均表现出良好的耐受性。在所有7例患者中均观察到皮肤疾病，如1/2级注射部位反应。尽管在5例患者（71.4%）中观察到可能由于同时接受放射性/替莫唑胺治疗导致的3级淋巴细胞减少症，但未观察到其他3/4级血液学或神经系统毒性。未观察到自身免疫反应。所有患者仍然存活，6例接受Wilms肿瘤1肽疫苗接种，无进展，组织学诊断的无进展生存期为5.2-49.1个月。在一名患者中，在12次注射后，根据患者的要求停止了Wilms肿瘤1肽疫苗接种。证实了用于治疗胶质母细胞瘤的组合的Wilms肿瘤1肽疫苗接种和替莫唑胺治疗方法的安全性特征。
To investigate the safety of combined Wilms tumor 1 peptide vaccination and temozolomide treatment of glioblastoma, a phase I clinical trial was designed. Seven patients with histological diagnosis of glioblastoma underwent concurrent radiotherapy and temozolomide therapy. Patients first received Wilms tumor 1 peptide vaccination 1 week after the end of combined concurrent radio/temozolomide therapy, and administration was continued once per week for 7 weeks. Temozolomide maintenance was started and performed for up to 24 cycles, and the observation period for safety encompassed 6 weeks from the first administration of maintenance temozolomide. All patients showed good tolerability during the observation period. Skin disorders, such as grade 1/2 injection-site reactions, were observed in all seven patients. Although grade 3 lymphocytopenia potentially due to concurrent radio/temozolomide therapy was observed in five patients (71.4 %), no other grade 3/4 hematological or neurological toxicities were observed. No autoimmune reactions were observed. All patients are still alive, and six are on Wilms tumor 1 peptide vaccination without progression, yielding a progression-free survival from histological diagnosis of 5.2-49.1 months. Wilms tumor 1 peptide vaccination was stopped in one patient after 12 injections by the patient's request. The safety profile of the combined Wilms tumor 1 peptide vaccination and temozolomide therapy approach for treating glioblastoma was confirmed.