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WT1 mRNA 负载树突状细胞瘤苗免疫治疗卵巢癌及癌肉瘤的免疫反应

Immunological response after WT1 mRNA-loaded dendritic cell immunotherapy in ovarian carcinoma and carcinosarcoma.

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 Sep;33(9):3855-9.

PMID:24023319
Abstract

BACKGROUND

Dendritic cell (DC)-based immunotherapy is an emerging new treatment option in ovarian cancer, an important cause of cancer-related mortality.

PATIENTS AND METHODS

One patient with ovarian carcinosarcoma (OCS) and one with serous ovarian cancer (SOC) received four weekly vaccinations of autologous DCs electroporated with mRNA coding for the Wilms' tumor gene 1 (WT1). Safety, feasibility and immunogenicity were assessed.

RESULTS

Vaccination was feasible without toxicity. In an ex vivo antigen re-stimulation assay of peripheral blood mononuclear cells, both patients showed increasing cluster of differentiation 137 (CD137+) antigen-specific T-cells and interleukin 10 (IL-10) production post-vaccination. Moreover, interleukin-2 (IL-2) production increased (OCS) as well as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) (SOC). Disease in patients progressed after four vaccines and patients continued with conventional therapies. After cessation of immunotherapy, they had an extended survival of 19 (OCS) and 12 (SOC) months.

CONCLUSION

To our knowledge, we report for the first time the feasibility and T-cell immunogenicity of WT1 mRNA-loaded DC immunotherapy in ovarian cancer.

摘要

背景

树突状细胞(DC)为基础的免疫疗法是卵巢癌的一种新兴治疗选择,卵巢癌是癌症相关死亡的一个重要原因。

患者和方法

一名卵巢癌肉瘤(OCS)患者和一名浆液性卵巢癌(SOC)患者接受了四次每周一次的自体树突状细胞接种,这些树突状细胞被编码Wilms 瘤基因 1(WT1)的 mRNA 电穿孔。评估了安全性、可行性和免疫原性。

结果

接种是可行的,没有毒性。在外周血单核细胞的体外抗原再刺激试验中,两名患者在接种后均显示出 CD137+抗原特异性 T 细胞和白细胞介素 10(IL-10)产生的增加。此外,白细胞介素 2(IL-2)的产生增加(OCS)以及干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)(SOC)。在四剂疫苗后,患者的疾病进展,他们继续接受常规治疗。免疫治疗停止后,他们的生存时间分别延长了 19 个月(OCS)和 12 个月(SOC)。

结论

据我们所知,我们首次报道了 WT1 mRNA 负载的 DC 免疫疗法在卵巢癌中的可行性和 T 细胞免疫原性。

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