Over the past decade, interest in using mRNA as a genetic blueprint to encode any therapeutic protein of interest in situ has dramatically boomed. At eTheRNA, we are dedicated to developing mRNA-based immunotherapies for the treatment of various malignancies, with TriMix mRNA being the frontrunner application. There are currently two clinical trials ongoing, investigating the potency of TriMix, a mixture of mRNAs that encodes potent immune stimulating molecules, CD40L, CD70 and caTLR4, which has been specifically designed to activate dendritic cells and to promote their interaction with T cells. In combination with mRNA encoding tumor-associated antigens (TAAs), TriMix acts as an adjuvant that enhances the TAA-specific T cell response.
The magnitude and functional characteristics of T cell responses elicited by mRNA vaccines are governed by the complex interplay between route of administration, delivery vehicle, and the intrinsic properties of the mRNA. Strong proof of concept of immunogenicity of intravenous administration of mRNA complexed into lipopolyplexes (LPR) has already been achieved, with the mRNA LPRs eliciting responses of unseen strength. Ongoing efforts focus on both finetuning the lipid composition for as on determining the optimal antigen to TriMix mRNA ratio. Besides acting an adjuvant in a vaccination context, TriMix mRNA can also act an immuno-modulator when applied directly into the tumor. Intratumoral administration of TriMix mRNA results in specific activation of dendritic cells in the tumor bed, which subsequently prime neo-epitope specific T cells and instigate systemic antitumor immunity.