دورية أكاديمية
Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy
| العنوان: | Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy |
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| المؤلفون: | Peishan Li, Ying Xie, Jinling Wang, Chunjie Bao, Jialun Duan, Yixuan Liu, Qian Luo, Jiarui Xu, Yuxin Ren, Min Jiang, Jianwei Li, Haitao Guo, Huihui Zhao, Guiling Wang, Yanqin Liang, Wanliang Lu |
| المصدر: | Bioactive Materials, Vol 34, Iss , Pp 466-481 (2024) |
| بيانات النشر: | KeAi Communications Co., Ltd., 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Materials of engineering and construction. Mechanics of materials LCC:Biology (General) |
| مصطلحات موضوعية: | Gene engineered exosomes, T cell exhaustion, PD1/PDL1, Imiquimod, Cancer immunotherapy, Materials of engineering and construction. Mechanics of materials, TA401-492, Biology (General), QH301-705.5 |
| الوصف: | Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8+ T cell with cancer cell, displaying a PD1/PDL1 immune checkpoint blockage effect, and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell, exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8+ T cell. In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2452-199X |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2452199X24000082; https://doaj.org/toc/2452-199X |
| DOI: | 10.1016/j.bioactmat.2024.01.008 |
| URL الوصول: | https://doaj.org/article/fb2dd4b5937b460992e27759f0844669 |
| رقم الأكسشن: | edsdoj.fb2dd4b5937b460992e27759f0844669 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2452199X |
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| DOI: | 10.1016/j.bioactmat.2024.01.008 |