DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation

Area of Science:

• Biomaterials Science
• Immunotherapy
• Nanotechnology

Background:

• Biomaterials are crucial for enhancing immunotherapy safety and efficacy.
• Precise control over biomaterial surface functionalization is key for immune cell modulation.
• Chimeric antigen receptor (CAR) T cell therapies require improved safety and targeted delivery.

Purpose of the Study:

• To develop biocompatible immune cell-engaging particles (ICEp) for tunable protein loading.
• To investigate the use of ICEp for enhancing CAR T cell therapy safety and efficacy.
• To explore the impact of ICEp surface functionalization on T cell activation.

Main Methods:

• Developed synthetic short DNA-based scaffolds for creating ICEp.
• Intratumoral injection of micrometre-sized ICEp to prime systemically administered AND-gate CAR-T cells.
• Functionalized ICEp with specific antigens, costimulatory ligands (anti-CD3, anti-CD28), and IL-2 cytokine.

Main Results:

• Locally retained ICEp successfully activated CAR T cells by presenting a high density of priming antigens.
• ICEp treatment led to local tumor clearance while sparing uninjected tumors in immunodeficient mice.
• Ratiometric control of costimulatory ligands and IL-2 presentation on ICEp significantly impacted human primary T cell activation.

Conclusions:

• ICEp represent a modular and versatile biomaterial platform for immunotherapy.
• This platform enables efficient and tunable protein loading for immune cell modulation.
• ICEp offer new opportunities for developing safer and more effective immunotherapies, particularly for CAR T cell treatments.