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树突状细胞介导的肿瘤相关抗原特异性细胞毒性T淋巴细胞治疗多发性骨髓瘤和非霍奇金淋巴瘤的临床研究

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma].

作者信息

Li Xiao-Han, Xue Lei, Xu Hui, Zhang Xu-Han, Liu Xin, Zhu Wei-Bo, Wang Xing-Bing

机构信息

Department of Hematology, Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China.

Department of Hematology, The First Affiliated Hospital of University of Sciences and Technoloty of China, Hefei 230001, Anhui Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Oct;28(5):1750-1756. doi: 10.19746/j.cnki.issn.1009-2137.2020.05.053.

Abstract

OBJECTIVE

To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lympho- cytes (TAA-CTL) in the treatment of multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).

METHODS

Peripheral blood mononuclear cells (PBMNC)of patients were collected. Dendritic cells (DC) were loaded with multiple tumor-associated antigens (TAA) (NY-ESO-1, MAGE-A3, MAGE-A4, WT1, Survivin, PRAME, LMP1 and LMP2A), then co-cultured with PBMNC to induce cytotoxic T lymphocytes (CTL). The phenotypes of cell products were detected, and the disease statuse was evaluated in 7 patients during or after infusion. The changes of TAA-CTL amount in the PBMNC of patients were measured by using IFN-γ ELISpot assay.

RESULTS

TAA-CTL products were generated comprising CD3 T cells (mean 82.98%) with a mixture of CD4 (mean 42.09%) and CD8 (mean 25.32%) T cells. Among them, 70% expressed effectors memory markers (CD45ROCD62LCCR7). Each patient received TAA-CTL infusions for 1-4 times, and none of them showed obvious adverse reactions. The clinical symptoms and laboratory or imaging examination of 5 patients achieved positive effects. After cell therapy, the spot-forming cells (SFC) levels of most patients gradually increased and the peak often appeared about 2-3 weeks after the infusion.

CONCLUSION

TAA-CTLs preliminarily show its safety and efficacy in MM and NHL patients, however, a larger population sample is needed to explore its clinical application value.

摘要

目的

探讨肿瘤相关抗原特异性细胞毒性T淋巴细胞(TAA-CTL)治疗多发性骨髓瘤(MM)和非霍奇金淋巴瘤(NHL)的安全性和有效性。

方法

采集患者外周血单个核细胞(PBMNC)。用多种肿瘤相关抗原(TAA)(NY-ESO-1、MAGE-A3、MAGE-A4、WT1、生存素、PRAME、LMP1和LMP2A)负载树突状细胞(DC),然后与PBMNC共培养以诱导细胞毒性T淋巴细胞(CTL)。检测细胞产物的表型,并在7例患者输注期间或输注后评估疾病状态。采用IFN-γ ELISpot试验检测患者PBMNC中TAA-CTL数量的变化。

结果

产生了TAA-CTL产物,其中包括CD3 T细胞(平均82.98%)以及混合的CD4(平均42.09%)和CD8(平均25.32%)T细胞。其中,70%表达效应记忆标志物(CD45ROCD62LCCR7)。每位患者接受TAA-CTL输注1-4次,均未出现明显不良反应。5例患者的临床症状及实验室或影像学检查取得了积极效果。细胞治疗后,大多数患者的斑点形成细胞(SFC)水平逐渐升高,峰值常出现在输注后约2-3周。

结论

TAA-CTL在MM和NHL患者中初步显示出其安全性和有效性,然而,需要更大的人群样本以探索其临床应用价值。

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