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.
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The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during the study are too large to be publicly shared, but they are available for research purposes from the corresponding authors on reasonable request. The raw sequence data in Supplementary Fig. 4 are available at the BioProject database under accession number PRJNA639217.
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This work was supported by the National Natural Science Foundation of China (grant nos. 21821005 and 21622608), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB29040303), the National Key R&D Program of China (grant no. 2017YFA0207900), the Science and Technology Program of Guangzhou, China (grant no. 201704020216), the Natural Science Foundation of Guangdong Province, China (grant no. 2018B030311042), and the Guangzhou Regenerative Medicine and Health Guangdong Laboratory, China (grant no. 2018GZR110105014).
The authors declare no competing interests.
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Xie, X., Hu, Y., Ye, T. et al. Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen. Nat Biomed Eng 5, 414–428 (2021). https://doi.org/10.1038/s41551-020-00624-6