Grant: Project Grant

When cytotoxic immune cells encounter a tumor they are excluded from entering it due to the dense protein environment that the tumor builds to evade being attacked. In this proposal, we will create personalized models of gastric cancer to study the mechanisms of how immune cells can overcome these barriers in order to migrate into the core of the tumor where the active cancer cells reside. We do this by creating gels obtained from patient tissues that we use to rebuild tumor models using cells isolated from the patient. By controlling the properties of the gel to replicate the immune exclusion of the tumor, we can determine how the activated immune cells are able to infiltrate into the tumor. To encourage the tumor to enter into a state where it is considered immune-active we propose to reprogramming the non-cancerous cells using RNA-loaded solid lipid nanoparticles that can remodel the dense protein gel. Currently, immune cell therapies have been shown to be highly effective in blood cancers, but their use in solid tumors such as gastric cancers has yet to be realized as the mechanisms that govern infiltration are not understood. The model we propose can catalyze the translation of these cell-based therapeutics into clinical use as it enables us to track the activity in a human-like tumor model.