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

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-Fc mRNA–LNP in OVCAR-5 and PC3 xenograft models significantly blocked the growth of not only local, treated tumors but also distant, untreated lesions.

In PC3 tumors, enhanced local and systemic antitumor activity of the combination treatment 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.