Intratumoral delivery of mRNA encoding the endogenous TLR2/6 agonist UNE-C1 induces immunogenic cell death and enhances antitumor activity

Our results advocate for the intratumoral delivery of UNE-C1 via mRNA therapy as a promising strategy for innovative antitumor treatments.

To address these challenges, our study focused on the intratumoral delivery of mRNA encoding UNE-C1, a TLR2/6 ligand known for its efficacy and low toxicity profile. We explored the potential of UNE-C1 to induce immunogenic cell death (ICD) through autocrine mechanisms, facilitated by the release of damage-associated molecular patterns (DAMPs) triggered by TLR2 activation.

Our findings indicate that sensitivity to UNE-C1-induced cell death is dependent on the expression levels of TLR2 and the Fas-associated death domain (FADD) in cancer cells. Furthermore, we investigated the paracrine activation of dendritic cells (DCs) by UNE-C1 via TLR2 signaling, which primes a CD8+ T cell response essential for tumor regression.