biostudies-literatureZhang LFundamental Research Funds for the Central UniversitiesNational High Level Hospital Clinical Research FundingCAMS Innovation Fund for Medical SciencesBeijing Nova ProgramNational Natural Science Foundation of Chinae12379https://www.ebi.ac.uk/biostudies/studies/S-EPMC10654473biostudies-literatureUnknown12(11)Dual targeting to immune checkpoints has achieved a better therapeutic efficacy than single targeting due to synergistic extrication of tumour immunity. However, most dual targeting strategies are usually antibody dependent which facing drawbacks of antibodies, such as poor solid tumour penetration and unsatisfied affinity. To meet the challenges, we engineered a cell membrane displaying a fusion protein composed of SIRPα and PD-1 variants, the high-affinity consensus (HAC) of wild-type molecules, and with which prepared nanovesicles (NVs). Through disabling both SIRPα/CD47 and PD-1/PD-L1 signalling, HAC NVs significantly preserved the phagocytosis and antitumour effect of macrophages and T cells, respectively. In vivo study revealed that HAC NVs had better tumour penetration than monoclonJournal of extracellular vesiclesEngineering high-affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy.PMC10654473BJ-2022-196822035342021-I2M-1-0502021-I2M-1-06620220484168E2ET5104X22237842952273281Ma XMa JZhang LYuan WZhao XNiu YfalseEngineering high-affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy.Dual targeting to immune checkpoints has achieved a better therapeutic efficacy than single targeting due to synergistic extrication of tumour immunity. However, most dual targeting strategies are usually antibody dependent which facing drawbacks of antibodies, such as poor solid tumour penetration and unsatisfied affinity. To meet the challenges, we engineered a cell membrane displaying a fusion protein composed of SIRPα and PD-1 variants, the high-affinity consensus (HAC) of wild-type molecules, and with which prepared nanovesicles (NVs). Through disabling both SIRPα/CD47 and PD-1/PD-L1 signalling, HAC NVs significantly preserved the phagocytosis and antitumour effect of macrophages and T cells, respectively. In vivo study revealed that HAC NVs had better tumour penetration than monoclon2023-01-01T00:00:00Z2023 Nov2026-06-02T01:23:00.248Z2025-04-19T13:50:26.871ZS-EPMC106544733797439510.1002/jev2.12379