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Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen
Nature Biomedical Engineering ( IF 28.1 ) Pub Date : 2020-10-12 , DOI: 10.1038/s41551-020-00624-6
Xiaoling Xie 1, 2 , Yuxing Hu 1 , Tong Ye 2, 3 , Yiran Chen 1 , Lijuan Zhou 1 , Feng Li 2, 3 , Xiaobo Xi 2, 3 , Shuang Wang 2 , Yanjie He 1 , Xiaoyong Gao 2 , Wei Wei 2, 3 , Guanghui Ma 2, 3 , Yuhua Li 1, 4
Affiliation  

Therapeutic leukaemia vaccines have shown modest potency. Here, we show that the co-encapsulation of a leukaemia-associated epitope peptide highly expressed in leukaemia patients and of the immune checkpoint inhibitor anti-programmed-cell-death-protein-1 (anti-PD-1) in degradable poly(lactic acid) microcapsules resulted in the sustained release of the peptide and of the antibody, which led to the recruitment of activated antigen-presenting cells to the injection site, their uptake of the peptide and the transportation of the anti-PD-1 antibody to lymph nodes, enhancing the expansion of epitope-specific T cells and the activation of cytotoxic T cells. After single subcutaneous injections of vaccine formulations with different epitope peptides, mice bearing leukaemia xenografts derived from humanized cell lines or from primary cells from patients showed better therapeutic outcomes than mice receiving repeated injections of free antigen, antibody and a commercial adjuvant. The sustained release of a tumour-associated peptide and of anti-PD-1 may represent a generalizable strategy for boosting antitumour immune responses to leukaemia.



中文翻译:

通过共包封的抗 PD-1 和白血病相关抗原的持续释放来对抗白血病的治疗性疫苗接种

治疗性白血病疫苗显示出适度的效力。在这里,我们展示了在白血病患者中高度表达的白血病相关表位肽和免疫检查点抑制剂抗程序性细胞死亡蛋白 1(抗 PD-1)在可降解聚乳酸酸)微胶囊导致肽和抗体的持续释放,这导致将激活的抗原呈递细胞募集到注射部位,它们摄取肽并将抗 PD-1 抗体转运至淋巴节点,增强表位特异性 T 细胞的扩增和细胞毒性 T 细胞的激活。在单次皮下注射具有不同表位肽的疫苗制剂后,与接受反复注射游离抗原、抗体和商业佐剂的小鼠相比,携带源自人源化细胞系或来自患者原代细胞的白血病异种移植物的小鼠显示出更好的治疗效果。肿瘤相关肽和抗 PD-1 的持续释放可能代表了增强对白血病的抗肿瘤免疫反应的普遍策略。

更新日期:2020-10-12
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