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

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.

Automated summary

In this study, co-encapsulation of a leukaemia-associated epitope peptide and anti-PD-1 antibody in degradable microcapsules led to sustained release and improved therapeutic outcomes in mouse models. The recruitment of activated antigen-presenting cells, expansion of epitope-specific T cells, and activation of cytotoxic T cells were enhanced by this strategy.