Intratumoral delivery of EpCAM-CD3-Fc bispecific antibody with IL-12 and GM-CSF mRNA-lipid nanoparticles (LNPs) blocks both local and distal tumor growth

ABSTRACT: Intratumoral delivery of mRNA–lipid nanoparticles (LNPs)–encoded bispecific antibodies and immunomodulatory proteins is a promising strategy for tumor eradication, offering potent local activity with limited toxicity and minimal systemic exposure. In this study, we evaluated two combinations of four immunostimulatory mRNAs and found that intratumoral administration of IL-2 and GM-CSF mRNA–LNPs together with EpCAM-CD3 mRNA–LNPs in OVCAR-5 and PC3 xenograft models significantly reduced not only treated tumors but also distant, untreated lesions. In PC3 tumors, enhanced local and systemic antitumor activity of the three-mRNA–LNP combination was associated with activation of T-cell–related pathways, as revealed by RNA-seq analysis. Key effector genes—including perforin (PRF1), granzyme H (GZMH), CD3E, CD3D, HLA-DPA1, among others—were upregulated following treatment with the bispecific antibody plus immunomodulator mRNA–LNPs, providing mechanistic support for the observed efficacy in both local and distant tumors. Collectively, these data demonstrate that intratumoral delivery of EpCAM-CD3 together with IL-2 and GM-CSF mRNA–LNPs represents a promising approach for future clinical investigation.

ORGANISM(S): Mus musculus

PROVIDER: GSE312815 | GEO | 2026/09/04

REPOSITORIES: GEO