Organ-specific delivery of an mRNA-encoded bispecific T cell engager targeting glypican-3 in hepatocellular carcinoma.

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 me

SUBMITTER: Huang Y 

PROVIDER: S-EPMC12705655 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature