In the heart of London, at King’s College London’s Institute of Pharmaceutical Science, a team of researchers led by Adam A. Walters has been making waves in the field of cancer immunotherapy. Their work, recently published in the journal *Small Science* (translated to English as “Small Science”), focuses on a novel approach to delivering RNA-based therapeutics using lipid nanoparticles (LNPs). This research could potentially reshape the landscape of cancer treatment and open new avenues for commercial applications in the biopharmaceutical industry.
The team’s breakthrough revolves around the use of ionizable lipid nanoparticles to deliver immunostimulatory polyinosinic-polycytidylic acid (pIpC). This synthetic analog of double-stranded RNA mimics a viral infection, triggering the immune system to attack cancer cells. “We’ve shown that pIpC can be successfully incorporated into LNPs with minimal modifications to existing protocols,” Walters explains. The resulting pIpC-LNPs are spherical, with a diameter under 200 nanometers, making them ideal for intratumoral administration.
The results are promising. When administered directly into tumors, pIpC-LNPs proved significantly more potent than the soluble adjuvant, leading to complete remission in 25% of tumors. This finding underscores the potential of LNPs as a versatile platform for delivering RNA-based therapeutics.
But Walters and his team didn’t stop there. They screened T cell activation markers following pIpC-LNP treatment and found that OX40 and CD27 were strongly upregulated, indicating potential synergistic targets. Interestingly, direct treatment of a cancer cell line with pIpC-LNPs also resulted in the upregulation of the immunosuppressive PDL1, suggesting a need for a comprehensive RNA-based immunotherapeutic strategy.
To address this, the team formulated LNPs with mRNAs encoding CD70 (the CD27 ligand) and OX40L, or with siRNA targeting PDL1, and evaluated them in combination with pIpC-LNPs. The results showed that tumor growth reduction was observed when pIpC-LNPs were combined with siPDL1.
This research demonstrates the potential of a triplet RNA platform—comprising immunostimulatory RNA, mRNA, and siRNA, all delivered via a single versatile LNP. “Our data support the development of pIpC-LNPs as potent intratumoral therapeutics and highlight several potential synergistic targets,” Walters notes.
The implications for the biopharmaceutical industry are substantial. The versatility of LNPs as a delivery platform could accelerate the development of new RNA-based therapies, opening up new markets and commercial opportunities. Moreover, the potential for combination therapies could lead to more effective treatments for a range of cancers, improving patient outcomes and driving growth in the oncology sector.
As the field of cancer immunotherapy continues to evolve, research like this is crucial. It not only advances our understanding of how to harness the immune system to fight cancer but also paves the way for innovative therapeutic strategies. With the publication of this work in *Small Science*, the stage is set for further exploration and development of this promising approach.
In the words of Walters, “This is just the beginning. The potential of RNA-based therapies is vast, and we’re excited to be at the forefront of this exciting field.” As the research community continues to build on these findings, the future of cancer treatment looks increasingly bright.