biostudies-literatureJiang TKey Basic Research Project of Shenzhen Science and Technology Research and Development FundNational Center for Technology Innovation in BiopharmaceuticalsGuangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine Talent Innovation TeamGuangxi Natural Science FoundationKey Area Research and Development Program of GuangDong ProvinceNational Natural Science Foundation of ChinaWellcome TrustShenzhen Science and Technology Programe17205https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499455biostudies-literatureUnknown12(37)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 synergAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Localized Delivery of the mRNAs Encoding CD47 Inhibitor and Interleukins 12, 15, and 21 Elicits Robust Antitumor Immunity.PMC12499455GZCX20231202KQTD202009091137580042022B1111050001NCTIB2022HS01005824609608227384122023JJA140431202414JCYJ20220818100402004Li HCai TJing SZhong XJiang TSun XWang JWei MWang PGLiang JHu HJi YJin JXiao BZhou JfalseLocalized Delivery of the mRNAs Encoding CD47 Inhibitor and Interleukins 12, 15, and 21 Elicits Robust Antitumor Immunity.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 synerg2025-01-01T00:00:00Z2025 Oct2026-06-04T04:43:35.536Z2026-05-05T03:12:22.026ZS-EPMC124994554065252210.1002/advs.202417205