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首页> 外文期刊>Gene therapy >The CD20/alphaCD20 'suicide' system: novel vectors with improved safety and expression profiles and efficient elimination of CD20-transgenic T cells.
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The CD20/alphaCD20 'suicide' system: novel vectors with improved safety and expression profiles and efficient elimination of CD20-transgenic T cells.

机译：CD20 / alphac20'自杀系统：具有改进的安全性和表达谱的新载体，有效地消除CD20-转基因T细胞。

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摘要

Adoptive transfer of T lymphocytes is an attractive strategy for many experimental treatment strategies for cancer. Unfortunately, manipulated T cells could be responsible for serious adverse events. Retroviral CD20-transduced T cells may be able to control these unwanted effects. CD20-positive cells are sensitive to rituximab (RTX), a monoclonal antibody specific for CD20. This permits their selective elimination in vivo in case of adverse events. To this end, a system is required that permits efficient and safe transduction of donor T cells and effective elimination of CD20-positive T cells. We constructed different CD20-encoding retroviral vectors and investigated the impact of inclusion of the woodchuck post-transcriptional regulatory element (WPRE) and the chicken hypersensitivity site 4 insulator elements on the levels, homogeneity and stability of CD20 expression. Importantly, inclusion of either WPRE or insulator elements in the retroviral vector resulted in a dramatic improvement in the stability of CD20 expression. The insulator element also led to a much more homogeneous level of CD20 expression. We also show the efficient elimination of the CD20-transgenic T cells via RTX by different effector mechanisms. In conclusion, we have constructed CD20-encoding retroviral vectors with improved efficiency and safety profiles, which can be used as a suicide strategy.
机译：患有T淋巴细胞的养态转移是癌症许多实验治疗策略的一种有吸引力的策略。不幸的是，操纵的T细胞可能负责严重的不良事件。逆转录病毒CD20-转导的T细胞可以能够控制这些不需要的效果。 CD20阳性细胞对Rituximab（RTX）敏感，所述CD20特异的单克隆抗体。这允许他们在不良事件时在体内选择性消除。为此，需要一种系统，其允许有效和安全地转导供体T细胞并有效地消除CD20阳性T细胞。我们构建了不同的CD20编码逆转录病毒载体，并研究了将柴火转录后调节元件（WPRE）和鸡超敏点部位4绝缘子元素纳入CD20表达的水平，均匀性和稳定性的影响。重要的是，包含逆转录病毒载体中的WPRE或绝缘体元件导致CD20表达稳定性的显着改善。绝缘体元件也导致了更加均匀的CD20表达水平。我们还通过不同的效应机制透过RTX展示了CD20-转基因T细胞的有效消除。总之，我们已经构建了CD20编码逆转录血管向量，其具有提高的效率和安全性曲线，可用作自杀策略。

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