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树突状细胞瘤苗联合 WT1 肽抗原对晚期非小细胞肺癌患者生存的影响。

Impact of dendritic cell vaccines pulsed with Wilms' tumour-1 peptide antigen on the survival of patients with advanced non-small cell lung cancers.

机构信息

Seren Clinic Tokyo, Tokyo, Japan.

出版信息

Eur J Cancer. 2013 Mar;49(4):852-9. doi: 10.1016/j.ejca.2012.11.005. Epub 2012 Dec 11.

Abstract

PURPOSE

Dendritic cell (DC)-based vaccines have been expected to serve as new therapeutic approaches for advanced non-small cell lung cancers (NSCLCs); however, their clinical outcomes have not been fully elucidated. We report a single-centre clinical study analysing factors affecting the survival of patients with advanced NSCLCs who received DC vaccines pulsed with or without Wilms' tumour protein-1 (WT1) peptide.

METHODS

Among 62 patients with previously treated inoperable or postoperatively relapsed NSCLCs who met the inclusion criteria, DCs from 47 (76%) patients who showed HLA-A2402/0201/0206 were pulsed with one or more corresponding WT1 peptide antigens. DC vaccines were intradermally injected biweekly.

RESULTS

Clinical responses based on response evaluation criteria in solid tumours (RECIST) were found in 31 (50%) patients at 3 months after the first DC vaccine (complete response: 1 (1.6%), partial response: 4 (6.5%), stable disease: 26 (41.9%)). Median survival time was 27 months (82% in 1 year and 54% in 2 years) from initial diagnosis, and that was 12 months (48% in 1 year and 22% in 2 years) from the first DC vaccination. Importantly, multivariate analyses revealed that only two factors, blood haemoglobin and the use of WT1 peptides, significantly affected the overall survival of patients from both initial diagnosis and first vaccination.

CONCLUSIONS

This study is the first to suggest that DC vaccines pulsed with WT1 may hold a significant impact to prolong the overall survival of patients with advanced NSCLCs.

摘要

目的

树突状细胞(DC)疫苗有望成为治疗晚期非小细胞肺癌(NSCLC)的新方法;然而,其临床结果尚未完全阐明。我们报告了一项单中心临床研究,分析了接受 WT1 肽负载或未负载的 DC 疫苗治疗的晚期 NSCLC 患者的生存影响因素。

方法

在符合纳入标准的 62 例既往治疗不可切除或术后复发的 NSCLC 患者中,47 例(76%)HLA-A2402/0201/0206 阳性的患者的 DC 被负载一个或多个相应的 WT1 肽抗原。DC 疫苗每两周皮内注射一次。

结果

首次 DC 疫苗接种后 3 个月,根据实体瘤反应评估标准(RECIST)发现 31 例(50%)患者有临床反应(完全缓解:1 例(1.6%),部分缓解:4 例(6.5%),稳定疾病:26 例(41.9%))。从初始诊断到中位无进展生存期为 27 个月(1 年时为 82%,2 年时为 54%),从首次 DC 疫苗接种到中位无进展生存期为 12 个月(1 年时为 48%,2 年时为 22%)。重要的是,多因素分析显示,只有两个因素,即血液血红蛋白和 WT1 肽的使用,显著影响了从初始诊断和首次接种疫苗开始的患者的总生存期。

结论

这项研究首次表明,负载 WT1 的 DC 疫苗可能对延长晚期 NSCLC 患者的总生存期有显著影响。

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