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WT1 基因负载树突状细胞瘤苗免疫治疗子宫肿瘤患者的Ⅰ/Ⅱ期临床试验。

Wilms' Tumor Gene 1 (WT1)--loaded dendritic cell immunotherapy in patients with uterine tumors: a phase I/II clinical trial.

机构信息

KU Leuven, Laboratory of Pediatric Immunology, Onderwijs & Navorsing 1, Herestraat 49 bus 811, 3000 Leuven, Belgium.

出版信息

Anticancer Res. 2013 Dec;33(12):5495-500.

PMID:24324087
Abstract

AIM

Treatment options are limited in uterine cancer, leading to a poor prognosis. Overexpression of Wilms' tumor gene 1 (WT1), the highest ranked tumor antigen, is attractive for immunotherapy.

PATIENTS AND METHODS

Six pre-treated patients with uterine cancer received four weekly vaccines of autologous dendritic cells (DCs) electroporated with WT1 mRNA. Safety, feasibility and immunogenicity were assessed. In cases of response, patients received monthly booster vaccines.

RESULTS

The technique was feasible. One patient had a local allergic reaction. Three out of four Human Leucocyte Antigen-A2 (HLA-A2)-positive patients showed an oncological response; an enrichment of WT1-specific T-cells was observed in two of them. Two HLA-A2-negative patients did not show an oncological or an immunological response.

CONCLUSION

A first series of six patients with uterine cancer treated with WT1 mRNA-electroporated DCs is presented herein. Oncological and immunological responses were observed and are supportive for further research.

摘要

目的

子宫癌的治疗选择有限,导致预后不良。Wilms 瘤基因 1(WT1)的过度表达,作为排名最高的肿瘤抗原,对于免疫治疗具有吸引力。

患者和方法

6 名接受过前期治疗的子宫癌患者接受了四次每周一次的自体树突状细胞(DC)电穿孔 WT1 mRNA 疫苗接种。评估了安全性、可行性和免疫原性。在有反应的情况下,患者接受每月的加强疫苗接种。

结果

该技术是可行的。一名患者出现局部过敏反应。四名 HLA-A2 阳性患者中的 3 名表现出肿瘤反应;其中 2 名观察到 WT1 特异性 T 细胞的富集。两名 HLA-A2 阴性患者未表现出肿瘤或免疫反应。

结论

本文介绍了首例 6 例子宫癌患者接受 WT1 mRNA 电穿孔树突状细胞治疗的情况。观察到了肿瘤和免疫反应,支持进一步研究。

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