IMPROVE: a feature model to predict neoepitope immunogenicity through broad-scale validation of T-cell recognition.

Background: Mutation-derived neoantigens are critical targets for tumor rejection in cancer immunotherapy, and better tools for neoepitope identification and prediction are needed to improve neoepitope targeting strategies. Computational tools have enabled the identification of patient-specific neoantigen candidates from sequencing data, but limited data availability has hindered their capacity to predict which of the many neoepitopes will most likely give rise to T cell recognition. Method: To address this, we make use of experimentally validated T cell recognition towards 17,500 neoepitope candidates, with 467 being T cell recognized, across 70 cancer patients undergoing immunotherapy. Results: We evaluated 27 neoepitope characteristics, and created a random forest model, IMPROVE, to predict neoepitope immunogenicity. The presence of hydrophobic and aromatic residues in the peptide binding core were the most important features for predicting neoepitope immunogenicity. Conclusion: Overall, IMPROVE was found to significantly advance the identification of neoepitopes compared to other current methods.

Lipid Nanoparticles for Delivery of Therapeutic RNA Oligonucleotides.

Gene therapy is an exciting field that has the potential to address emerging scientific and therapeutic tasks. RNA-based gene therapy has made remarkable progress in recent decades. Nevertheless, efficient targeted delivery of RNA therapeutics is still a prerequisite for entering the clinics. In this review, we introduce current delivery methods for RNA gene therapeutics based on lipid nanoparticles (LNPs). We focus on the clinical appeal of recent RNA NPs and discuss existing challenges of fabrication and screening LNP candidates for effective translation into drugs of human metabolic diseases and cancer.