Engineering high-affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy

Area of Science:

• Biomaterials Engineering
• Immunotherapy
• Nanotechnology

Background:

• Dual immune checkpoint targeting improves anti-tumour immunity compared to single-target strategies.
• Antibody-based therapies face limitations in solid tumour penetration and binding affinity.

Purpose of the Study:

• To engineer a novel nanovesicle (NV) system for dual targeting of immune checkpoints.
• To overcome the limitations of antibody-dependent therapies using a cell membrane-based fusion protein delivery system.

Main Methods:

• Engineered nanovesicles displaying a fusion protein of SIRPα and PD-1 variants (HAC).
• Assessed the dual blockade of SIRPα/CD47 and PD-1/PD-L1 signalling pathways.
• Evaluated in vivo tumour penetration, binding affinity, therapeutic efficacy, and biosafety.

Main Results:

• HAC NVs preserved macrophage phagocytosis and T cell anti-tumour effects.
• HAC NVs demonstrated superior tumour penetration and binding affinity compared to monoclonal antibodies and wild-type NVs.
• Dual blockade of CD47 and PD-L1 using HAC NVs showed significant therapeutic efficacy and biosafety.

Conclusions:

• Developed a novel biomaterial for overcoming tumour immune escape.
• Presented an effective biomimetic technology for multi-targeting protein delivery.
• HAC NVs offer a promising strategy for enhanced cancer immunotherapy.