Revolutionizing Liver Cancer Treatment with Advanced Therapeutic Delivery Systems

Our research aims to develop advanced methods for delivering the cytokine LIGHT directly to liver tumors in high concentrations, which could significantly enhance its therapeutic potential when combined with immunotherapies like anti-CTLA4. Systemic injection of soluble cytokines presents challenges such as a short half-life, off-target effects, and toxicity, making it an impractical approach. Thus, innovative macroscopic and microscopic delivery systems are essential to overcome these limitations and achieve effective, targeted delivery of LIGHT.

The liver's unique dual blood supply—primarily fed by the hepatic artery in colorectal liver metastases (CRLM)—offers a distinct advantage for targeted therapies. Physicians have already leveraged this by using hepatic artery infusion (HAI) to deliver higher concentrations of chemotherapy directly to liver tumors, increasing treatment efficacy while minimizing systemic side effects. This makes HAI an ideal system for regional delivery of LIGHT. However, in order to utilize this approach, we must optimize the microscopic delivery of LIGHT to prevent degradation in the serum before it reaches its target Currently, mRNA delivery systems such as lipid nanoparticles (LNPs) have proved effective and safe, as evidenced by the COVID-19 vaccine. Therefore, LNPs may be an efficient and clinically available approach to deliver LIGHT into the tumor microenvironment (TME). Our lab will be combining these technologies to treat CRLM by injecting clinical grade LIGHT mRNA encapsulated LNPs into the hepatic artery of mice with CRLM. We hypothesize that this method will enable more effective tumor targeting and potentially revolutionize the treatment of patients with unresectable CRLM, setting the stage for future clinical trials.