In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma
In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma
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DOI：
10.1111/j.1365-2141.2007.06754.x
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发表时间：
2007-10-01
影响因子：
6.5
通讯作者：
Lu, Zhao Yang
中科院分区：
文献类型：
--
作者：
Burjanadze, Maka;Condomines, Maud;Lu, Zhao Yang
T细胞介导的免疫治疗是多发性骨髓瘤（MM）的一种有前途的治疗选择。γ-δ T细胞（γ δ T细胞）识别磷抗原并显示出强的抗肿瘤细胞毒性。合成激动剂Phosphortim（溴醇焦磷酸盐，BrHPP）已被证明可以选择性激活V gamma 9V delta 2 T细胞。本研究旨在使用磷酸盐和白细胞介素2（IL-2）评价MM患者在疾病期间不同时间点的循环γ δ T细胞的扩增能力和抗骨髓瘤细胞毒性。新诊断MM或复发患者的循环γ δ T细胞计数与健康供体无差异。在78%的新诊断患者中，用磷酸盐和IL-2培养外周血单个核细胞14天，引发γ δ T细胞扩增100倍。在造血祖细胞收集时或在复发患者中收集的γ δ T细胞扩增效率较低。扩增的γ δ T细胞杀死13/14骨髓瘤细胞系以及原代骨髓瘤细胞，但不杀死正常的CD 34细胞。IL-2饥饿2天对它们的杀伤效率没有影响。该研究证明了磷酸化和IL-2扩增来自MM患者的γ δ T细胞的能力，以及gd T细胞对人骨髓瘤细胞的有效和稳定杀伤。
T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (gamma delta T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate V gamma 9V delta 2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating gamma delta T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating gamma delta T cell counts in patients with newly diagnosed MM or in relapse did not differ from those in healthy donors. A 14-d culture of peripheral blood mononuclear cells with Phosphostim and IL-2 triggered a 100-fold expansion of gamma delta T cells in 78% of newly diagnosed patients. gamma delta T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded gamma delta T cells killed 13/14 myeloma cell lines as well as primary myeloma cells, but not normal CD34 cells. Their killing efficiency was not affected by 2-d IL-2 starvation. This study demonstrated the ability of Phosphostim and IL-2 to expand gamma delta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.