AUTHOR=Liu Yuxuan , Yang Fuxu , Li Zhimin , Wang Ting , Mu Yeteng , Fan Yuxin , Xue Han , Hu Xiuli , Guan Xingang , Feng Hongxia TITLE=Concurrent immune checkpoint blockade for enhanced cancer immunotherapy utilizing engineered hybrid nanovesicles JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1487940 DOI=10.3389/fphar.2024.1487940 ISSN=1663-9812 ABSTRACT=

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, demonstrating unprecedented efficacy against advanced cancers. However, their clinical applications are significantly hampered by low overall response rates. Dual blockade of two immune checkpoints represents a promising strategy to enhance immunotherapeutic efficacy. In this study, we developed hybrid cell membrane nanovesicles adorned with PD-1 and SIRPα receptors for combination immunotherapy in melanoma. Our hybrid nanovesicles (PD-1/SIRPα NVs) demonstrated high specificity to PD-L1 and CD47 ligands, facilitating the phagocytosis of melanoma cells by macrophages. In a melanoma mouse model, PD-1/SIRPα NVs significantly suppressed 77% of tumor growth and elicited a robust antitumor immune response for immunotherapy. In conclusion, our findings highlight the promising potential of PD-1/SIRPα NVs as novel and effective ICIs for cancer immunotherapy.