Chemical Artificial Internalizing Receptors for Primary T Cells,Advanced Science

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Chemical Artificial Internalizing Receptors for Primary T Cells
Advanced Science ( IF 14.3 ) Pub Date : 2020-07-26 , DOI: 10.1002/advs.202001395
Pere Monge ₁ , Anne Tvilum ₁ , Ane Bretschneider Søgaard ₁ , Kaja Borup Løvschall ₁ , Morten T Jarlstad Olesen _{1,

2} , Alexander N Zelikin _{1,

2}

Affiliation

The newest generation of cell‐based technologies relies heavily on methods to communicate to the engineered cells using artificial receptors, specifically to deactivate the cells administered to a patient in the event of adverse effects. Herein, artificial synthetic internalizing receptors are engineered that function in mammalian cells in 2D and in 3D and afford targeted, specific intracellular drug delivery with nanomolar potency in the most challenging cell type, namely primary, donor‐derived T cells. Receptor design comprises a lipid bilayer anchor for receptor integration into cell membrane and a small xenobiotic molecule as a recognition ligand. Artificial receptors are successfully targeted by the corresponding antibody–drug conjugate (ADC) and exhibit efficient cargo cell entry with ensuing intracellular effects. Receptor integration into cells is fast and robust and affords targeted cell entry in under 2 h. Through a combination of the receptor design and the use of ADC, combined benefits previously made available by chimeric artificial receptors (performance in T cells) and the chemical counterpart (robustness and simplicity) in a single functional platform is achieved. Artificial synthetic receptors are poised to facilitate the maturation of engineered cells as tools of biotechnology and biomedicine.

中文翻译：

原代 T 细胞的化学人工内化受体

最新一代的基于细胞的技术在很大程度上依赖于使用人工受体与工程细胞进行通信的方法，特别是在发生不良反应时使给予患者的细胞失活。在此，人工合成的内化受体被设计成在哺乳动物细胞中以 2D 和 3D 的方式发挥作用，并在最具挑战性的细胞类型（即原代供体来源的 T 细胞）中提供具有纳摩尔效力的靶向、特异性细胞内药物递送。受体设计包括用于将受体整合到细胞膜中的脂质双层锚和作为识别配体的小异生分子。人工受体成功地被相应的抗体药物偶联物 (ADC) 靶向，并表现出有效的货物细胞进入能力以及随后的细胞内效应。受体与细胞的整合快速而稳定，并在 2 小时内即可进入目标细胞。通过受体设计和 ADC 的使用相结合，实现了先前通过嵌合人工受体（T 细胞中的性能）和化学对应物（稳健性和简单性）在单一功能平台中提供的综合优势。人工合成受体有望作为生物技术和生物医学的工具，促进工程细胞的成熟。

更新日期：2020-09-23

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