Chemical Artificial Internalizing Receptors for Primary T Cells

Area of Science:

• Biotechnology
• Cellular Engineering
• Drug Delivery

Background:

• Cell-based therapies require methods for controlling engineered cells, particularly for deactivation during adverse events.
• Existing methods for cell communication and control have limitations in specific cell types like T cells.

Purpose of the Study:

• To engineer artificial synthetic internalizing receptors for mammalian cells.
• To achieve targeted, specific intracellular drug delivery with high potency in primary T cells.
• To create a robust and simple functional platform combining benefits of previous receptor technologies.

Main Methods:

• Engineered synthetic receptors with a lipid bilayer anchor and xenobiotic recognition ligand.
• Utilized antibody-drug conjugates (ADCs) for targeted receptor engagement.
• Tested receptor function in 2D and 3D mammalian cell cultures, including primary T cells.

Main Results:

• Achieved nanomolar potency for intracellular drug delivery in primary T cells.
• Demonstrated fast (under 2 hours) and robust receptor integration and cell entry.
• Successfully targeted receptors with ADCs, leading to efficient cargo delivery and intracellular effects.
• Combined the performance of chimeric artificial receptors with the robustness of chemical counterparts.

Conclusions:

• Artificial synthetic internalizing receptors provide a powerful platform for controlling engineered cells.
• This technology facilitates targeted intracellular drug delivery and cell deactivation.
• The developed system is poised to advance the use of engineered cells in biotechnology and biomedicine.