ArticleNature communications2025
Organ-specific delivery of an mRNA-encoded bispecific T cell engager targeting glypican-3 in hepatocellular carcinoma.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Alantolactone inhibits T-cell lymphoma progression by suppressing CD47 expression via the PI3K/AKT and ERK signaling pathways.Apoptosis : an international journal on programmed cell death · 2026Article
- A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection.Journal of hematology & oncology · 2026Article
- Vitamin A-coupled MSCs- derived extracellular vesicles relieve acute liver injury by targeting hepatic stellate cells to deliver REDD1.Journal of nanobiotechnology · 2026Article
- Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026Review
- Single injection of modified self-amplifying RNA encoding a CD19 bispecific T cell engager mediates long-term malignant B cell clearance.bioRxiv : the preprint server for biology · 2026Article
- Co-delivering macrophage engager mRNA and PD-L1 antibody via tumor-responsive nanoparticles for glioblastoma immunotherapy.Nature communications · 2026Article
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
- Lipid nanoparticles and extracellular vesicles: emerging cell free therapeutic platforms for hepatobiliary cancers.Frontiers in cell and developmental biology · 2026Review
- From Lab to Clinic: How Artificial Intelligence (AI) Is Reshaping Drug Discovery Timelines and Industry Outcomes.Pharmaceuticals (Basel, Switzerland) · 2025Review
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Authors and funding
24 authors.
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Abstract
T-cell engager (TCE)-based immunotherapy is clinically validated in hematological cancers. However, application in solid tumors faces hurdles including T cell penetration, the immunosuppressive tumor microenvironment, and toxicity. We develop an mRNA-encoded TCE (MTS105) targeting Glypican-3, the hepatocellular carcinoma antigen, delivered via lipid nanoparticles directly to liver tissue. In mice, rats, and cynomolgus monkeys, MTS105 exhibits higher liver exposure versus plasma. Liver-orthotopic tumor-bearing mice achieve complete, dose-dependent regression, with fast intratumoral T cell activation owing to sustained higher liver and tumor functional TCE exposure versus conventional antibody-based TCE. In vivo, MTS105 induces intratumoral CD8 cell precursor and terminally differentiated memory subsets with high activation scores. In cynomolgus monkeys, MTS105 displays favorable, linear plasma pharmacokinetics including mRNA, ionizable lipid, and translated TCE following single and repeated-four-weekly dosing (up to 45 μg/kg). No severe adverse effects or gross pathology were observed. Our results thus support the advancement of MTS105 into clinical trials, with a first-in-human study currently underway.
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