Co-delivering macrophage engager mRNA and PD-L1 antibody via tumor-responsive nanoparticles for glioblastoma immunotherapy - PubMed
3 hours ago
- #Macrophage Engager
- #Glioblastoma Immunotherapy
- #Nanoparticle Delivery
- Developed PL@mBiME, a multifunctional lipid nanoparticle (LNP) platform for glioblastoma immunotherapy.
- Co-delivers mRNA encoding a bispecific macrophage engager (BiME) and PD-L1 antibody via tumor-responsive nanoparticles.
- BiME targets ErbB2 on glioma cells and CD206 on M2 macrophages, reprogramming macrophages to pro-inflammatory M1 phenotype.
- Enhances macrophage-tumor cell bridging, tumor cell phagocytosis, and antigen presentation.
- Incorporates pH-responsive charge reversal for improved tumor accumulation and lysosomal escape.
- Utilizes glutathione-triggered release of surface-conjugated PD-L1 antibody to amplify anti-tumor immunity.
- Activates both innate and adaptive immunity, inducing tumor regression, prolonged survival, and durable immune memory without significant toxicity.