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Non-viral transfection technologies for next-generation therapeutic T cell engineering

机译：下一代治疗性T细胞工程的非病毒转染技术

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摘要

Genetically engineered T cells have sparked interest in advanced cancer treatment, reaching a milestone in 2017 with two FDA-approvals for CD19-directed chimeric antigen receptor (CAR) T cell therapeutics. It is becoming clear that the next generation of CAR T cell therapies will demand more complex engineering strategies and combinations thereof, including the use of revolutionary gene editing approaches. To date, manufacturing of CAR T cells mostly relies on gamma-retroviral or lentiviral vectors, but their use is associated with several drawbacks, including safety issues, high manufacturing cost and vector capacity constraints. Non-viral approaches, including membrane permeabilization and carrier-based techniques, have therefore gained a lot of interest to replace viral transductions in the manufacturing of T cell therapeutics. This review provides an in-depth discussion on the avid search for alternatives to viral vectors, discusses key considerations for T cell engineering technologies, and provides an overview of the emerging spectrum of non-viral transfection technologies for T cells. Strengths and weaknesses of each technology will be discussed in relation to T cell engineering. Altogether, this work emphasizes the potential of non-viral transfection approaches to advance the next-generation of genetically engineered T cells.
机译：转基因T细胞引发了对晚期癌症治疗的兴趣，2017年达到了一个里程碑，具有两种FDA认证，用于CD19针对嵌合抗原受体（CAR）T细胞治疗剂。很明显，下一代汽车T细胞疗法将需要更复杂的工程策略及其组合，包括使用革命性基因编辑方法。迄今为止，汽车T细胞的制造主要依赖于γ-逆转录病毒或慢病毒载体，但它们的使用与几个缺点相关，包括安全问题，高制造成本和矢量容量限制。因此，非病毒方法，包括膜透化和基于载体的技术，因此替代T细胞治疗剂的制造中的病毒转导。本次审查提供了关于AVID搜索对病毒载体的替代品的深入讨论，讨论了T细胞工程技术的关键考虑，并概述了T细胞的非病毒转染技术的新出现谱。将关于T细胞工程讨论各技术的优势和弱点。完全，这项工作强调了非病毒转染方法的潜力，以推进下一代转基因T细胞。

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