The discovery of mRNA therapy that eradicates tumors in preclinical trials

Etherna, a biotech company pioneering mRNA and lipid-based-nanoparticle (LNP) technologies, has announced the publication of pre-clinical data showing the therapeutic potential of a new mixture of mRNA-encoded immune modulators designed to activate the immune system to eradicate tumors.

The study, published in Nature Communications and conducted in collaboration with the researchers from the Vlaams Instituut voor Biotechnology (VIB) Vrije Universiteit Brussel (VUB) and Universiteit Gent (UGent), highlights the unique potential of etherna’s mRNA and LNP platforms to yield improved anti-cancer immunotherapies.

The study revealed that a combination of three mRNAs (named “Triplet”) encoding for the cytokines IL-21 and IL-7 and the membrane-bound co-stimulator 4-1BBL (named Triplet) acts synergistic in stimulating anti-tumor T cells and evoking regression of injected and distal tumors upon LNP-mediated intratumoral injection.

Notably, the triplet combination showed remarkable efficacy in triple-negative breast cancer, an aggressive disease with limited treatment options. In these models, the therapy achieved an 85% tumor regression rate.

Additionally, the triplet therapy proved effective in immune checkpoint blockade-resistant cancer models, showcasing its potential to overcome resistance to existing immunotherapy treatments. Early translational steps confirmed that the LNP-encapsulated Triplet mRNA can be successfully expressed by myeloid and tumor cells derived from non-small cell lung carcinomas, indicating potential applicability in human clinical settings.

mRNA-based immunotherapy has garnered significant attention for its ability to stimulate the immune system to recognize and destroy cancer cells. However, challenges such as mRNA instability, rapid degradation, and poor cellular uptake have hindered its clinical potential. etherna’s mRNA-LNP technology addresses these obstacles, providing a robust delivery platform to maximize therapeutic efficacy. 

Dr. Florence Lambolez, Pharmacology Director at etherna, highlighted the potential, “The ability to achieve robust preclinical results while taking early steps toward human applicability demonstrates the promise of our platform. We’re committed to advancing these therapies toward clinical trials and, ultimately, improving outcomes for patients battling hard-to-treat cancers.”

Dr. Stefaan De Koker, VP Technology and Innovation at etherna, added, “These results validate the versatility and effectiveness of our immunotherapeutic platform. In addition to screening many combinations of cytokines and co-stimulators to arrive at the Triplet mix, advanced mRNA sequence engineering and LNP optimization were needed to achieve robust anti-tumor efficacy. The platform's adaptability allows us to tailor therapeutic mRNAs to meet the unique challenges of various cancers."

Want the latest science news straight to your inbox? Become a SelectScience member for free today>>