Identification of a TCR to a non-canonical peptide (NCP) presented by the autologous non-small cell lung cancer (NSCLC) following an immunotherapy that includes canonical and NCPs 3338

作者：Tarsem Moudgil, Traci Hilton, Olivier Fesneau, Yi-Ping Shih, Christopher Paustian, Noah D. Simons, Yoshinobu Koguchi, Venkatesh Rajamanickam, Ryan Meng, Brady Bernard, Noriko Iwamoto, Yuriko Minegishi, Koji Ueda, Brenda Fisher, Blake L. Tsu, Stefanie N. Kairs, Chris Barnes, William L. Redmond, Takashi Shimada, Carlo Bifulco, Hong‐Ming Hu, Eric Tran, Walter J. Urba, Thomas Duhen, Rom S. Leidner, Rui Li, Rachel E. Sanborn, Bernard A. Fox · 发表于：The Journal of Immunology · 年份：2025 · DOI：10.1093/jimmun/vkaf283.1154 · 被引用次数：1 · 研究领域：vaccines and immunoinformatics approaches、Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers

Abstract Description Background NCPs derived from non-coding regions of the genome are a recently discovered source of non-mutated HLA-presented cancer antigens. Here we studied the immune response of a patient with NSCLC that received adjuvant treatment with DPV-001 immunotherapy that contained canonical and non-canonical antigens. The patient is disease free at 10 years. Materials and Methods This patient received 7 doses of DPV-001 at 3-week intervals. PBMCs and serum were collected regularly to assess antibodies (PhIPseq), peripheral lymphocytes populations (flow cytometry), and TCR repertoires. A metastasis resected 5 months into treatment generated a tumor cell line and tumor-infiltrating lymphocyte (TIL) culture. The HLA-presented immunopeptidome of the patient’s NSCLC cell line was characterized by mass spectrometry and identified more than 300 NCP from 5’UTR. Antibody responses to the canonical protein downstream of the 5’UTR were used to prioritize peptides for detection of a T cell response in TIL. The TCR of a responding T cell was identified, expressed, and evaluated. Results The identified TCR recognized a NCP and autologous NSCLC cell line, it was not detected pretreatment. Current studies are evaluating whether this TCR recognizes other cancer cell lines. Conclusions The detection of a T cell response to a NCP presented by the patient’s cancer expands the range of possible cancer antigens that can be targeted with the potential to improve outcomes for patients...