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首页> 外文期刊>Expert opinion on biological therapy >Gene-modified T lymphocytes in the setting of hematopoietic cell transplantation: potential benefits and possible risks.
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Gene-modified T lymphocytes in the setting of hematopoietic cell transplantation: potential benefits and possible risks.

机译：在造血细胞移植中使用基因修饰的T淋巴细胞：潜在的好处和可能的风险。

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INTRODUCTION: Allogeneic hematopoietic cell transplantation (HCT) is a consolidated treatment for several hematologic malignancies. Donor T lymphocytes can mediate a graft versus tumor (GVT) effect and control opportunistic infections but can also cause severe graft versus host disease (GVHD). Gene-transfer strategies are appealing tools to modulate T cell functions when infused after HCT. AREAS COVERED: The current and potential future applications of T cell gene-transfer approaches to HCT. This review is not limited to GVHD control but covers the issues of GVT and immune reconstitution. Clinical data are used to discuss more general issues, perspectives and concerns common to gene-modification of T cells. An overview of the results and limitations emerging from clinical trials with herpes simplex virus-thymidine kinase (HSV-TK) engineered lymphocytes is provided. The review provides perspectives on additional gene-transfer strategies, currently at preclinical level or that have just entered clinical trials, to increase the efficacy and safety of HCT. EXPERT OPINION: Gene-transfer can positively interfere with T cell functions after HCT. TK-lymphocytes have proven effective in controlling GVHD while retaining an acceptable GVT effect. Strategies exploiting new suicide molecules or engineered T cell receptors (TCRs) should be further explored to address current limitations with TK-lymphocytes and augment the efficacy and specificity of GVT and antiviral activity.
机译：简介：同种异体造血细胞移植（HCT）是对几种血液系统恶性肿瘤的综合治疗。供体T淋巴细胞可介导移植物抗肿瘤（GVT）作用并控制机会性感染，但也可引起严重的移植物抗宿主病（GVHD）。基因转移策略是在HCT注入后调节T细胞功能的诱人工具。覆盖的领域：T细胞基因转移方法在HCT中的当前和潜在的未来应用。这篇综述不仅限于GVHD控制，还涵盖了GVT和免疫重建的问题。临床数据用于讨论T细胞基因修饰常见的一般问题，观点和关注点。提供了对单纯疱疹病毒-胸苷激酶（HSV-TK）工程淋巴细胞的临床试验结果和局限性的概述。该综述提供了有关其他基因转移策略的观点，这些策略目前处于临床前水平或刚刚进入临床试验，以提高HCT的疗效和安全性。专家意见：基因转移可以对HCT后的T细胞功能产生积极影响。 TK淋巴细胞已被证明可有效控制GVHD，同时保持可接受的GVT效果。应该进一步探索开发新的自杀分子或工程化的T细胞受体（TCR）的策略，以解决TK淋巴细胞当前的局限性，并提高GVT的功效和特异性以及抗病毒活性。

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