Scholarlink

<p>Bispecific immune cell engagers, particularly bispecific T-cell engagers, show limited efficacy in solid tumors such as glioblastoma (GBM) due to systemic toxicities, poor T cell infiltration, and restricted drug penetration. We develop PL@mBiME, a multifunctional lipid nanoparticle (LNP) platform that enables brain tumor–targeted delivery and sustained in vivo expression of mRNA encoding a bispecific macrophage engager (BiME). The BiME simultaneously targets ErbB2 on glioma cells and CD206 on M2 macrophages, reprogramming macrophages toward pro-inflammatory M1 phenotype while promoting macrophage–tumor cell bridging, enhancing tumor cell phagocytosis and antigen presentation. PL@mBiME incorporates pH-responsive charge reversal to improve tumor accumulation and lysosomal escape as well as glutathione-triggered release of surface-conjugated PD-L1 antibody to amplify anti-tumor immunity. Across multiple GBM models, this coordinated activation of innate and adaptive immunity induces tumor regression, prolongs survival, and generates durable immune memory without significant toxicity.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Co-delivering macrophage engager mRNA and PD-L1 antibody via tumor-responsive nanoparticles for glioblastoma immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月11日

查看全文
  • Haoge Zhang,
  • Jia Miao,
  • Lin Gao,
  • Xuhong Yang,
  • Zhengcheng Yun,
  • Lei Dong,
  • Wanqing Cheng,
  • Yuqi Wang,
  • Hui Yang,
  • Ying Zhou,
  • Yini Zhu,
  • Jinbing Xie

摘要

Bispecific immune cell engagers, particularly bispecific T-cell engagers, show limited efficacy in solid tumors such as glioblastoma (GBM) due to systemic toxicities, poor T cell infiltration, and restricted drug penetration. We develop PL@mBiME, a multifunctional lipid nanoparticle (LNP) platform that enables brain tumor–targeted delivery and sustained in vivo expression of mRNA encoding a bispecific macrophage engager (BiME). The BiME simultaneously targets ErbB2 on glioma cells and CD206 on M2 macrophages, reprogramming macrophages toward pro-inflammatory M1 phenotype while promoting macrophage–tumor cell bridging, enhancing tumor cell phagocytosis and antigen presentation. PL@mBiME incorporates pH-responsive charge reversal to improve tumor accumulation and lysosomal escape as well as glutathione-triggered release of surface-conjugated PD-L1 antibody to amplify anti-tumor immunity. Across multiple GBM models, this coordinated activation of innate and adaptive immunity induces tumor regression, prolongs survival, and generates durable immune memory without significant toxicity.