Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy
Abstract 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 pen...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-11-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12379 |
| _version_ | 1797503373808762880 |
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| author | Luyao Zhang Xu Zhao Yanan Niu Xiaoya Ma Wei Yuan Jie Ma |
| author_facet | Luyao Zhang Xu Zhao Yanan Niu Xiaoya Ma Wei Yuan Jie Ma |
| author_sort | Luyao Zhang |
| collection | DOAJ |
| description | Abstract 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 monoclonal antibodies and higher binding affinity to CD47 and PD‐L1 on tumour cells compared with the NVs expressing wild‐type fusion protein. Exhilaratingly, dual‐blockade of CD47 and PD‐L1 with HAC NVs exhibited excellent therapeutic efficacy and biosafety. This study provided a novel biomaterial against tumoural immune escape and more importantly an attractive biomimetic technology of protein delivery for multi‐targeting therapies. |
| first_indexed | 2024-03-10T03:49:42Z |
| format | Article |
| id | doaj.art-5bf3015b2615414a8c3ec5b9fae11747 |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-03-10T03:49:42Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-5bf3015b2615414a8c3ec5b9fae117472023-11-23T09:00:37ZengWileyJournal of Extracellular Vesicles2001-30782023-11-011211n/an/a10.1002/jev2.12379Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapyLuyao Zhang0Xu Zhao1Yanan Niu2Xiaoya Ma3Wei Yuan4Jie Ma5Center of Biotherapy, Beijing Hospital, National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaCenter of Biotherapy, Beijing Hospital, National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing ChinaAbstract 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 monoclonal antibodies and higher binding affinity to CD47 and PD‐L1 on tumour cells compared with the NVs expressing wild‐type fusion protein. Exhilaratingly, dual‐blockade of CD47 and PD‐L1 with HAC NVs exhibited excellent therapeutic efficacy and biosafety. This study provided a novel biomaterial against tumoural immune escape and more importantly an attractive biomimetic technology of protein delivery for multi‐targeting therapies.https://doi.org/10.1002/jev2.12379cellular nanovesicleshigh‐affinity consensusimmune checkpoint blockadePD‐1/PD‐L1protein engineeringSIRPα/CD47 |
| spellingShingle | Luyao Zhang Xu Zhao Yanan Niu Xiaoya Ma Wei Yuan Jie Ma Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy Journal of Extracellular Vesicles cellular nanovesicles high‐affinity consensus immune checkpoint blockade PD‐1/PD‐L1 protein engineering SIRPα/CD47 |
| title | Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy |
| title_full | Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy |
| title_fullStr | Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy |
| title_full_unstemmed | Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy |
| title_short | Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy |
| title_sort | engineering high affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy |
| topic | cellular nanovesicles high‐affinity consensus immune checkpoint blockade PD‐1/PD‐L1 protein engineering SIRPα/CD47 |
| url | https://doi.org/10.1002/jev2.12379 |
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