Ion channelome of solid tumours: Novel immunotherapy targets for cancer-specific mRNA and drug delivery

Objective

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. While immunotherapies have revolutionised care for a small subset of patients, the vast majority remain resistant due to immunologically “cold” tumours and the lack of effective delivery systems for RNA therapies. ION-CANDEL addresses this urgent unmet need through a first-in-class precision platform that combines novel targets, advanced nanomedicine, and immune modulation into a single therapeutic strategy. The project will map and validate CRC-enriched ion channel variants as unique molecular “fingerprints” using single-cell and long-read sequencing supported by proteomics. These variants will serve as precision “locks” for engineering short peptide–decorated, thermo-responsive lipid nanoparticles (LNPs). The platform will then be armed with a combinatorial RNA cargo—a pro-apoptotic mRNA and an anti-PD-L1 siRNA—to trigger tumour cell death and restore immune activity. Preclinical validation in 2D/3D cultures and mouse models will establish tumour targeting, safety, and therapeutic efficacy. ION-CANDEL is directly aligned with the MSCA work programme: it advances frontier science through an interdisciplinary workflow, provides the researcher fellow with cutting-edge training in nanomedicine and immuno-oncology, and generates open-access resources, reproducible workflows, and exploitable intellectual property. By uniting discovery with translational application, it strengthens Europe’s leadership in RNA/LNP therapeutics and supports the researcher fellow’s path towards independence as a translational oncology group leader. Through scientific excellence, societal relevance, and economic potential, ION-CANDEL promises to transform precision oncology for CRC patients while consolidating the fellow’s career and Europe’s capacity to innovate in next-generation RNA therapies.