Chemical Artificial Internalizing Receptors for Primary T Cells

Pere Monge, Anne Tvilum, Ane Bretschneider Søgaard, Kaja Borup Løvschall, Morten T. Jarlstad Olesen, Alexander N. Zelikin*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

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.

Original languageEnglish
Article number2001395
JournalAdvanced Science
Volume7
Issue18
Number of pages8
DOIs
Publication statusPublished - 2020

Keywords

  • antibody–drug conjugates
  • artificial receptors
  • cell engineering
  • endocytosis

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