Overall Component: Project Summary/Abstract The overall goal of CAP-IT Center for RNA Immunoprevention (CRI) is to pre-clinically delineate, formulate and validate liponanoparticle RNA (LNP RNA) vaccines for precision prevention of individuals with increased cancer risk. The PI is Dr. Lipkin, an established leader in Cancer Prevention who has made several important, clinically translated contributions to the field. Project 1 will develop and validate an LNP RNA immunoprevention vaccine for Lynch syndrome, a genetic cancer predisposition syndrome with highly immunogenic recurrent neoantigens shared among cancers from different patients. Project 2 will develop and validate an LNP RNA immune interception vaccine for patients with lung non-solid nodule (NSN) pre-malignant neoplasms, a lung adenocarcinoma precursor lesion. To achieve these goals, we will use state-of-the-art technologies, including LNP RNA vaccine formulation, computational genomic tumor immunology, spatial genomics and immunopeptidomics. To ensure CRI's scientific rigor and excellence, we have assembled a scientifically outstanding CRI External Advisory Board (EAB), which includes 2021 Lasker Award winner Drew Weissman (Penn) for his work on LNP RNA COVID19 vaccines. Overall, the CAP-IT CRI will develop state-of-the-art LNP RNA immunoprevention and immune interception vaccines and provide a technologically powerful platform to jumpstart additional CAP-IT CRI LNP RNA vaccine projects. We anticipate that CAP-IT CRI will propel both Lynch syndrome and lung NSN vaccines to NCI PREVENT and CP-NET clinical trials within the next 5 years and FDA approval/clinical translation within ten years.

Overall Component: Project Narrative Advances in medical sciences led to the elucidation of infectious disease mechanisms and clinical translation of potent vaccines and therapies to reduce the death burden from common infections such as polio, meningococcus, and many others that are now almost forgotten in the US because of these successes. Today, in the early 21st century, we are building on the remarkable advances in our mechanistic understanding of the genomic architecture of cancer and its predisposition. The CAP-IT CRI will focus on recent rapid advances in RNA vaccine technology, cancer immune prevention, and interception vaccines that have the potential to substantially reduce the cancer burden in the 21st century.