Discovery of Human Papilloma Virus and patient-specific neoantigens targeted by CD8+ T cells in HNSCC

Abstract Head and neck squamous cell carcinoma (HNSCC) is amongst the rapidly growing form of cancer associated with high mutation burden Human Papilloma virus (HPV) infection presenting approximately 800,000 new cases 400,000 deaths annually. HPV-positive HNSCC has been strongly better prognosis than HPV-negative due to immune activation in tumor microenvironment including cytotoxic CD8+ T cells. One key missing links relative contribution HPV-reactive neoantigen-reactive cells anti-tumor response. To address this, we utilized epitope libraries presented Signaling Antigen-presenting Bifunctional Receptors (SABRs), which were previously described by our lab. As a proof-of-concept, generated SABR 8392 epitopes derived from HPV or personalized neoantigens five patients. In parallel, used single RNA sequencing identify 25 clonally expanded TCRs tumor-infiltrating lymphocytes Using screens, have identified several putative HPV-derived neoantigen-derived targeted We established robust pipeline for identification patient-specific specificities The goal determine whether how effective anti-HPV anti-neoantigen responses may contribute therapeutic efficacy using human samples clinical trials murine models. Our study will aid discovery novel tumor-associated antigens HPV+ patients, can be successfully employed precise adoptive transfer therapies.