Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen

作者：Xie, Xiaoling; Hu, Yuxing; Ye, Tong; Chen, Yiran; Zhou, Lijuan; Li, Feng; Xi, Xiaobo; Wang, Shuang; He, Yanjie; Gao, Xiaoyong; Wei, Wei^*; Ma, Guanghui^*; Li, Yuhua^*

来源：Nature Biomedical Engineering, 2021, 5(5): 414-+.

DOI：10.1038/s41551-020-00624-6

• ACUTE MYELOID-LEUKEMIA
• PEPTIDE VACCINE
• WT1 EXPRESSION
• RESPONSES
• LYMPHOCYTES
• GENERATION
• TRANSPLANTATION
• IMMUNOTHERAPY
• INHIBITION
• BLOCKADE

The sustained release of a leukaemia-associated epitope peptide and of anti-PD-1 antibody co-encapsulated in degradable microcapsules results in superior therapeutic outcomes in mouse models of leukaemia. @@@ 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.

• 单位
  南方医科大学; 中国科学院; 中国科学院研究生院