Abstract 6622: The identification of extranodal NK/T cell lymphoma-associated antigen for helper T cell-based immunotherapy

Abstract

Abstract Extranodal natural killer/T-cell lymphoma, nasal type (NKTL) is a fatal destructive tumor that develops around the nasopharyngeal and nasal/paranasal areas. Although this disease was originally considered to be endemic to East Asia, Central and South America and was extremely rare in Europe and the United States, the incidence of NKTL has increased during the last several decades in countries where it was previously not epidemic. The combination of irradiation and chemotherapies such as SMILE and MPVIC-P are effective. However, these therapies cause severe and sometimes fatal adverse effects indicating that a novel strategy to treat NKTL is required. The positive results of clinical trials using immune checkpoint inhibitors in solid tumors proved that immune cells are capable of eliminating tumor. However, autoimmune diseases are inevitable adverse events in this type of therapy, which non-specifically activates T cells. Thus, the identification of epitope peptides in tumor has re-emerged as an attractive concept. I will describe our study to identify NKTL-derived T cell epitopes as a basis of cancer vaccine. The expression of c-Met and its ligand HGF plays a critical role in cell proliferation and is involved in numerous malignancies. Because c-Met expression and its role in NKTL remain unclear, we first studied the expression and function of c-Met in NKTL cells. As a result, we found that HGF and c-Met were expressed and contributed to the proliferation of cells in NK/T-cell lymphoma. Next, the helper epitopes were identified from c-Met protein using computer-based algorism. The identified epitope peptides could elicit peptide-specific helper CD4 T cells (HTLs), which showed antitumor responses in vitro. The addition of c-Met inhibitor suppressed TGF-β production from tumor followed by the augmentation of HTL responses. In summary, we identified novel c-Met HTL epitopes that can elicit effective antitumor responses against tumors expressing c-Met. Our results provide the rationale of combining c-Met targeting therapy and immunotherapy for NKTCLs and epithelial tumors. Citation Format: Takumi Kumai, Ryusuke Hayashi, Tatsuya Hayashi, Hiroya Kobayashi, Yasuaki Harabuchi. The identification of extranodal NK/T cell lymphoma-associated antigen for helper T cell-based immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6622.