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多种肽段致敏树突状细胞联合诱导特异性细胞毒性 T 淋巴细胞治疗实体瘤患者的安全性和抗肿瘤作用。

The safety and anti-tumor effect of multiple peptides-pulsed dendritic cells combined with induced specific cytotoxic T lymphocytes for patients with solid tumors.

机构信息

Biotherapy Center & Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Front Immunol. 2023 Oct 24;14:1284334. doi: 10.3389/fimmu.2023.1284334. eCollection 2023.

Abstract

OBJECTIVE

The aim of this study was to explore the safety and efficacy of multiple peptide-pulsed autologous dendritic cells (DCs) combined with cytotoxic T lymphocytes (CTLs) in patients with cancer.

METHODS

Five patients diagnosed with cancer between November 2020 and June 2021 were enrolled and received DC-CTLs therapy. Peripheral blood was collected and antigenic peptides were analyzed. The phenotype and function of DC-CTLs and the immune status of patients were detected using flow cytometry or IFN-γ ELISPOT analysis.

RESULTS

DCs acquired a mature phenotype and expressed high levels of CD80, CD86, CD83, and HLA-DR after co-culture with peptides, and the DC-CTLs also exhibited high levels of IFN-γ. Peripheral blood mononuclear cells from post-treatment patients showed a stronger immune response to peptides than those prior to treatment. Importantly, four of five patients maintained a favorable immune status, of which one patient's disease-free survival lasted up to 28.2 months. No severe treatment-related adverse events were observed.

CONCLUSION

Our results show that multiple peptide-pulsed DCs combined with CTLs therapy has manageable safety and promising efficacy for cancer patients, which might provide a precise immunotherapeutic strategy for cancer.

摘要

目的

本研究旨在探讨多种肽脉冲自体树突状细胞(DCs)联合细胞毒性 T 淋巴细胞(CTLs)治疗癌症患者的安全性和有效性。

方法

2020 年 11 月至 2021 年 6 月期间,5 名癌症患者入组并接受 DC-CTLs 治疗。采集外周血并分析抗原肽。采用流式细胞术或 IFN-γ ELISPOT 分析检测 DC-CTLs 的表型和功能以及患者的免疫状态。

结果

DCs 在与肽共培养后获得成熟表型,并高表达 CD80、CD86、CD83 和 HLA-DR,DC-CTLs 也高表达 IFN-γ。治疗后患者外周血单个核细胞对肽的免疫反应强于治疗前。重要的是,5 名患者中有 4 名保持了良好的免疫状态,其中 1 名患者的无病生存期长达 28.2 个月。未观察到严重的治疗相关不良事件。

结论

我们的研究结果表明,多种肽脉冲 DCs 联合 CTLs 治疗具有可管理的安全性和对癌症患者有良好的疗效,为癌症提供了一种精确的免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7e/10628471/1d9e0ab2ba76/fimmu-14-1284334-g001.jpg

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