Vaccines that prime a patient’s own immune system to attack cancer are an attractive strategy, with the potential to promote durable regression of cancer that is not subject to rapid treatment resistance. However, to date cancer vaccines have generally failed in two important ways to optimally target cancer: First, cancer vaccines have typically targeted proteins that are over-expressed by tumor cells but not necessarily unique to tumor cells- this can lead to poor potency and the danger of autoimmune reactions. Second, vaccines based on peptides, proteins, or whole cell lysates have generally shown poor immunogenicity in patients, due in part to poor uptake of such vaccines by the immune system. We propose the translational development of a novel vaccine platform that addresses these two key limitations and could further be combined with promising immunomodulators such as checkpoint blockade therapies in patients to promote potent but safe anti-tumor immunity. In collaboration with the Broad Institute and the Dana Farber Cancer Institute (DFCI), we are pursuing cancer vaccines that are generated by sequencing the genome of individual patient tumors, and then forming vaccines that are chemically designed to traffic to lymph nodes following injection. We will carry out preclinical safety and manufacturing studies to enable clinical trials of this concept, which has shown great promise in small animal models of cancer therapy. We hypothesize that combining these two promising cancer vaccine technologies will lead to a highly potent, patient-targeted cancer vaccine strategy that could be broadly applied to diverse tumors.