The transformative potential of lipid nanoparticles tailored for acute myeloid leukemia immunotherapy

T-cell engagers and engineered cell therapies have yet to deliver the same spectacular results in acute myeloid leukemia (AML) that they have in other hematologic malignancies. In this review, we analyze the challenges with AML immunotherapy development, including on-target, off-tumor toxicity, cytokine release syndrome (CRS), and the "myeloid sink." We then discuss the emergence of two technologies that could address the major challenges with investigational AML therapeutics: targeted, lipid nanoparticles (LNPs) loaded with specific mRNAs and a type of synthetic logic gate (a NOT gate). This approach builds on recent advancements of mRNA-loaded LNPs that developed with the COVID19 vaccines and evolved into vehicles for delivery to T cells. The LNP modality offers a new opportunity for effective treatment of patients with AML.