In situ generation of anti-leukemia vaccine by immunogenic dual-drug nanomedicine and polymersomal CpG nanoadjuvant.

Acute myeloid leukemia (AML) is difficult to treat because of the difficulty in completely removing leukemia cells. Therapeutic vaccines that show promise in curing different cancers have achieved relatively little progress in the treatment of AML. Herein, we report the facile in situ generation of an anti-AML vaccine via an immunogenic vincristine/volasertib dual-drug nanomedicine (nanoVi/Vo) and a polymersomal CpG immunoadjuvant (nanoCpG). NanoVi/Vo boosted the generation of diverse tumor antigens by inducing immunogenic cell death (ICD) while synergistically inhibiting the growth of AML cells. Combining nanoVi/Vo with nanoCpG provoked a strong vaccination effect, which efficiently promoted dendritic cell (DC) maturation and facilitated T-cell activation and infiltration in the bone marrow, eliciting strong antitumor immunity in an orthotopic WEHI-3-Luc AML model. Notably, nanoVi/Vo combined with nanoCpG substantially suppressed leukemia progression in the bone marrow and infiltration to other organs, resulting in a significant survival benefit, with 57% of the mice surviving. This in situ vaccine generation strategy has promising potential as an effective immunotherapy approach for AML.