Affiliations
- Center of Biotherapy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing, China.
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PMID: 37974395 PMCID: PMC10654473 DOI: 10.1002/jev2.12379
Abstract
Background: Dual targeting of immune checkpoints can enhance therapeutic efficacy over single targeting due to synergistic effects on tumor immunity. This study explores a novel strategy using nanovesicles (NVs) engineered with a high-affinity consensus (HAC) of SIRPα and PD-1 variants.
Methods: HAC NVs were designed to inhibit SIRPα/CD47 and PD-1/PD-L1 interactions, preserving macrophage and T-cell antitumor activities. The efficacy of HAC NVs was evaluated in vivo and compared to monoclonal antibodies.
Results: HAC NVs displayed improved tumor penetration, higher binding affinity, and superior therapeutic efficacy against tumors compared to monoclonal antibodies. They also demonstrated excellent biosafety.
Conclusions: This study introduces a promising biomimetic approach for multi-targeting cancer immunotherapy using engineered NVs, providing a novel solution to enhance tumor immunity.
Keywords
PD-1/PD-L1; SIRPα/CD47; cellular nanovesicles; high-affinity consensus; immune checkpoint blockade; protein engineering.
