伊米奎莫德
免疫系统
CD8型
免疫疗法
医学
癌症免疫疗法
癌症研究
免疫检查点
佐剂
癌症
T细胞
树突状细胞
外体
癌细胞
黑色素瘤
免疫学
内科学
微泡
生物
基因
生物化学
小RNA
作者
Peishan Li,Ying Xie,Jinling Wang,Chun-Jie Bao,Jingli Duan,Yixuan Liu,Qian Luo,Jiaxi Xu,Yi Ren,Min Jiang,Jianwei Li,Hongwei Guo,Huihui Zhao,Guiling Wang,Yanqin Liang,Wan-Liang Lü
标识
DOI:10.1016/j.bioactmat.2024.01.008
摘要
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.
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