树突状细胞介导的肿瘤相关抗原特异性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：李晓晗 薛磊 徐慧[2] 张旭晗 刘欣[2] 朱薇波 王兴兵 LI Xiao-Han;XUE Lei;XU Hui;ZHANG Xu-Han;LIU Xin;ZHU Wei-Bo;WANG Xing-Bing(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)

机构地区：[1]安徽医科大学附属省立医院血液科,安徽合肥230001 [2]中国科学技术大学附属第一医院血液科,安徽合肥230001

出　　处：《中国实验血液学杂志》2020年第5期1750-1756,共7页Journal of Experimental Hematology

基　　金：安徽省科技重大专项(18030801126);安徽省科技攻关项目(1604a0802071)。

摘　　要：目的:初步探究靶向肿瘤相关抗原特异性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:采集患者自身外周血单个核细胞(PBMNC),使用含有多种肿瘤相关抗原(TAA)(NY-ESO-1,MAGE-A3,MAGE-A4,WT1,Survivin,PRAME,LMP2A和LMP1)的混合多肽,负载树突状细胞(DC),刺激共培养细胞毒性T细胞(CTL),测定细胞产物表型,并对7例回输后的患者进行病情评估。同时,利用IFN-γELISpot试验检测输注前、后患者外周血中TAA-CTL含量的变化。结果:平均82.98%的TAA-CTL产物为CD3^+T细胞,包括42.09%的CD4^+T细胞和25.32%的CD8^+T细胞,其中70%表达效应记忆标记(CD45RO^+CD62L^-CCR7^-)。每例患者接受1-4次TAA-CTL回输,均无明显不良反应;5例患者的临床症状、实验室检查或影像学检查提示一定的疗效;细胞治疗后,患者外周血斑点形成细胞(SFC)数高峰期常出现在输注后2-3周左右。结论:TAA-CTL初步显示了其对MM和NHL患者的安全性和有效性,但还需更大样本量以探讨其临床应用价值。Objective:To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lymphocytes(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 LMP2 A),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 TAACTL amount in the PBMNC of patients were measured by using IFN-γELISpot assay.Results:TAA-CTL products were generated comprising CD3^+T cells(mean 82.98%)with a mixture of CD4^+(mean 42.09%)and CD8^+(mean25.32%)T cells.Among them,70%expressed effectors memory markers(CD45 RO^+CD62 L^-CCR7^-).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 spotforming 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.

关 键 词：肿瘤相关抗原特异性T淋巴细胞 免疫治疗 多发性骨髓瘤 非霍奇金淋巴瘤 

分 类 号：R733.1[医药卫生—肿瘤] R733.3[医药卫生—临床医学]