CD5⁺ dendritic cell robots mediated in situ immunocyte activation

Area of Science:

• Biomedical Engineering
• Immunotherapy
• Nanotechnology

Background:

• Current immune cell therapies face challenges like systemic inflammation and functional exhaustion.
• Ex vivo activation and adoptive transfer of cytotoxic immune cells have limitations.
• A need exists for targeted, stable, and effective immune cell delivery systems.

Purpose of the Study:

• To develop a novel CD5+ dendritic cell microbot (CD5+DC robot) for targeted cancer therapy.
• To engineer natural CD5+ dendritic cells to create self-propelling and navigating microbots.
• To establish a system that activates durable antitumor immunity by reprogramming the tumor microenvironment.

Main Methods:

• CD5+ dendritic cells were engineered to phagocytose magnetic nanoparticles coated with tumor cell membranes.
• PD-L1 on CD5+ cells was preblocked to enhance immune activation.
• Magnetic fields were used to control microbot clustering (chain-like for upstream, ribbon-like for downstream) for precise vascular navigation.
• Microbots navigated tumor chemokine gradients and infiltrated tumor tissues via chemotaxis.

Main Results:

• CD5+DC robots demonstrated precise aggregation at intestinal targets via magnetic field control.
• Microbots successfully infiltrated deep into tumor tissues by navigating chemokine gradients.
• The CD5+DC robot system activated cascading immune responses and reprogrammed innate immune cells within the tumor microenvironment.
• This approach induced durable antitumor immunity, distinct from traditional cytotoxic therapies.

Conclusions:

• The developed CD5+DC robot system offers a novel strategy for precision-targeted cancer therapy.
• This microbot system exhibits excellent biocompatibility and functional stability.
• Reprogramming innate immune cells within the tumor microenvironment is a viable pathway for durable antitumor immunity.