Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, P R China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P R China.
Nat Biomed Eng. 2021 May;5(5):414-428. doi: 10.1038/s41551-020-00624-6. Epub 2020 Oct 12.
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.
治疗性白血病疫苗显示出一定的效力。在这里，我们表明，将在白血病患者中高度表达的白血病相关表位肽与免疫检查点抑制剂抗程序性细胞死亡蛋白-1（抗 PD-1）共同包封在可降解的聚乳酸微胶囊中，可导致肽和抗体的持续释放，从而招募活化的抗原呈递细胞到注射部位，摄取肽并将抗 PD-1 抗体运输到淋巴结，从而增强表位特异性 T 细胞的扩增和细胞毒性 T 细胞的激活。在用不同表位肽的疫苗制剂进行单次皮下注射后，携带来自人源化细胞系或来自患者的原代细胞的白血病异种移植物的小鼠的治疗效果优于接受游离抗原、抗体和商业佐剂重复注射的小鼠。肿瘤相关肽和抗 PD-1 的持续释放可能代表一种可推广的策略，可增强对白血病的抗肿瘤免疫反应。
