Manufacturing synthetic viscoelastic antigen-presenting cells for immunotherapy

Area of Science:

• Biomaterials Science
• Immunology
• Microfluidics

Background:

• Natural antigen-presenting cells (APCs) are crucial for T cell activation in immunotherapy.
• Existing synthetic APCs often lack the tunable physical and biochemical properties of natural APCs.
• Mimicking natural APCs is key to enhancing immunotherapeutic efficacy.

Purpose of the Study:

• To detail a protocol for fabricating and functionalizing viscoelastic synthetic APCs.
• To create cell-sized microbeads with tunable stiffness and viscoelasticity.
• To optimize synthetic APCs for enhanced T cell activation and immunotherapeutic applications.

Main Methods:

• Utilizing a high-throughput microfluidic system for fabricating sodium alginate microbeads.
• Employing crosslinking strategies to control mechanical properties (stiffness, viscoelasticity).
• Surface functionalization via click chemistry for attaching activation molecules and characterization of properties.

Main Results:

• Synthetic APCs precisely mimic natural APC physical and activation properties.
• Achieved enhanced T cell activation, expansion, and CD8/CD4 T cell ratio.
• Demonstrated improved CAR T cell transduction efficiency and superior tumor-killing efficacy.
• Showcased efficient removal of synthetic APCs post-activation.

Conclusions:

• This protocol provides a robust platform for engineering synthetic APCs with tunable properties.
• The developed synthetic APCs significantly improve T cell-mediated immune responses and therapeutic potential.
• This approach offers a versatile tool for immune cell engineering and immunotherapy development.