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首页> 外文期刊>International immunopharmacology >Trastuzumab enhanced the cytotoxicity of V gamma 9V delta 2 T cells against zoledronate-sensitized osteosarcoma cells
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Trastuzumab enhanced the cytotoxicity of V gamma 9V delta 2 T cells against zoledronate-sensitized osteosarcoma cells

机译：曲妥珠单抗增强了Vγ9Vδ2 T细胞对唑来膦酸盐致敏的骨肉瘤细胞的细胞毒性

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Preliminary studies of V gamma 9V delta 2 T cells and zoledronate (ZOL) present promising reasons to exploit their immunotherapeutic potential for osteosarcoma treatment (OS). ZOL is a third-generation aminobisphosphonate (ABP) and is well established in the management of cancer-induced bone disease. However, ZOL is characterized by high tropism for bone matrix, and the efficacy of ZOL for sensitizing tumors remains to be optimized. V gamma 9V delta 2 T cells are important effectors of antibody-dependent cell-mediated cytotoxicity (ADCC). In this study, we investigated whether V gamma 3V delta 2 T cell-mediated killing of ZOL-pretreated OS cells could be increased by the anti-HER-2 monoclonal antibody trastuzumab (TTZ). The cytotoxic activity of V gamma 9V delta 2 T cells against osteosarcoma was assessed by an MTS assay in the presence or absence of TIZ. A CD107a assay was used to measure degranulation in cytotoxic V gamma 9V delta 2 T cells. Blocking studies were used to determine the effect of relative ligands on V gamma 9V delta 2 T cell recognition. ITZ induced an ADCC response in the OS cell line, U2OS; however, it had no effect on another OS cell line HOS with low levels of surface HER2 expression. Although the OS cells pretreated with ZOL for clinically relevant time periods (2 hours) stimulated a suboptimal immune response of V gamma 9V delta 2 T cells, TTZ could further enhance the cytotoxicity of V gamma 9V delta 2 T cells. These results demonstrate that combining TTZ and ZOL significantly increases the cytotoxic potential of V gamma 9V delta 2 T cells. This study raises the possibility of utilizing ZOL and TIZ in V gamma 9V delta 2 T cell-based immunotherapy for OS. (C) 2015 Elsevier B.V. All rights reserved.
机译：Vγ9Vδ2 T细胞和唑来膦酸盐（ZOL）的初步研究提出了有希望的理由，以开发它们的免疫治疗潜力来治疗骨肉瘤（OS）。 ZOL是第三代氨基双膦酸盐（ABP），在治疗癌症引起的骨病方面已广为确立。然而，ZOL的特征是骨基质具有高向性性，并且ZOL致敏肿瘤的功效仍有待优化。 V gamma 9V delta 2 T细胞是抗体依赖性细胞介导的细胞毒性（ADCC）的重要效应子。在这项研究中，我们调查了抗HER-2单克隆抗体曲妥珠单抗（TTZ）是否可以提高Vγ3Vδ2 T细胞介导的ZOL预处理OS细胞的杀伤。在存在或不存在TIZ的情况下，通过MTS分析评估了V gamma 9V delta 2 T细胞对骨肉瘤的细胞毒活性。 CD107a分析用于测量细胞毒性V gamma 9V delta 2 T细胞中的脱颗粒。使用阻断研究来确定相对配体对Vγ9Vδ2 T细胞识别的影响。 ITZ在OS细胞系U2OS中诱导了ADCC响应。然而，它对具有低水平表面HER2表达的另一种OS细胞系HOS没有影响。尽管用ZOL预处理临床相关时间段（2小时）的OS细胞刺激了Vγ9Vδ2 T细胞的次优免疫反应，但TTZ可以进一步增强Vγ9Vδ2 T细胞的细胞毒性。这些结果表明，将TTZ和ZOL组合使用可显着增加V gamma 9V delta 2 T细胞的细胞毒性潜力。这项研究提出了在基于Vγ9V delta 2 T细胞的OS免疫疗法中使用ZOL和TIZ的可能性。 （C）2015 Elsevier B.V.保留所有权利。

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