Localized Delivery of the mRNAs Encoding CD47 Inhibitor and Interleukins 12, 15, and 21 Elicits Robust Antitumor Immunity.

ABSTRACT: CD47 inhibitors have emerged as promising candidates in cancer immunotherapy by activating macrophage phagocytosis through CD47/SIRPα signal blockade and enhancing dendritic cell antigen presentation. However, their clinical efficacy remains limited and is accompanied by severe side effects, including anemia and hemagglutination. To address these limitations, a localized delivery strategy is developed using lipid nanoparticles to encapsulate mRNA encoding a secreted CD47 inhibitor. This mRNA-derived CD47 inhibitor effectively activated macrophages against cancer cells in vitro. To improve its modest tumor-suppressive effects in vivo, a combination therapy is formulated by co-delivering mRNAs encoding the CD47 inhibitor and a cytokine cocktail (interleukins 12, 15, and 21), achieving synerg

SUBMITTER: Jiang T 

PROVIDER: S-EPMC12499455 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature