The idea: Our group has developed a patented vaccine made from genetic material (RNA) from the tumor itself, and combines with nanoparticles (NPs) that can be delivered intravenously to the blood stream (mRNA-NPs). We have demonstrated that “personalized” mRNA-NPs can help the immune system fight cancer cells and make standard immunotherapy treatments work better. We are currently using this vaccine in human clinical trials in brain cancer. We are now designing a first-ever mRNA-NP human clinical trial to be run here at the Cleveland Clinic Taussig Cancer Institute, for patients with recurrent head and neck cancer (HNSCC). As we design our trial, we want to establish the most effective vaccine formulations and combinations with other immunotherapy treatments. Specifically, we want to study mRNANP vaccines that can target human papilloma virus (HPV) viral antigens. If this formulation is found to be as effective (or more) that our “personalized” vaccine approach, we can treat patients with HPV-associated cancers more broadly with an “off-the-shelf” vaccine. Additionally we want to learn from patients samples why certain immune cells make these aggressive tumors resist standard treatments, so we can better formulate targets for the vaccine.