{
  "abstract": "Background Neoantigens—tumor-specific peptides arising from somatic alterations—offer a promising path for individualized immunotherapy. Recent studies have highlighted the potential of non-canonical cancer antigens—targets derived from the dark genome and other unconventional sources—as novel immunogenic epitopes beyond conventional SNV-derived neoantigens. To enable comprehensive identification of such diverse neoantigens, we developed a novel, whole-genome sequencing (WGS)-driven bioinformatics pipeline designed to identify high-confidence neoantigens in solid tumors. This pipleline is being deployed in support of an upcoming clinical trial of personalized cancer vaccines.Methods Building on prior work where we successfully validated immunogenicity prediction tools for SNV-derived neoantigens in solid tumors, 1 we have extended our pipeline to detect neoantigens arising from a broader array of genomic alterations, including splice variants and exon-transposon junctions. The pipeline integrates tumor-normal WGS and RNA-seq data to identify somatic variants and aberrant tanscripts. Neoantigen candidates undergo expression filtering, HLA-binding prediction, clonality analysis, and immune tolerance assessment to prioritize those most likely to elicit a T-cell response.Results We are analyzing WGS and RNA-seq data from 1,067 patients with solid tumors recruited to the National Whole-Genome Project in Japan. An initial application of the pipeline to a cohort of 43 breast cancer and 167 sarcoma patients demonstrated its capacity to identify a diverse and individualized set of neoantigens, including previously underexplored epitopes arising from exon-transposon junctions. These novel neoantigen classes substantially expanded the immunogenic landscape, leading to the discovery of highly immunogenic candidates beyond those derived from canonical SNVs. This expansion of the antigenic repertoire supports a more comprehensive and personalized vaccine design strategy. Additional analyses in other cancer types are currently in progress.Conclusions Our original WGS-based neoantigen discovery pipeline represents a powerful platform for next-generation personalized immunotherapy in solid tumors. By capturing a wide mutational spectrum—including exon-transposon junctions—our approach enhances the likelihood of identifying clinically relevant, immunogenic targets. The pipeline is now in active use to guide vaccine design for a clinical trial in solid tumors, representing a major step toward individualized treatment strategies for this high-need population.Acknowledgements This research was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Number JP24ck0106869.Reference Le Tourneau C, Delord JP, Lalanne A, e t al. Randomized phase I trial of adjuvant individualized TG4050 vaccine in patients with locally advanced resected HPV-negative head and neck squamous cell carcinoma (HNSCC). J Immunother Cancer. 2024;12.Ethics Approval This study was approved by the Institutional Review Board of the Cancer Institute Hospital of the Japanese Foundation for Cancer Research (2021-GB-006, 2024-GB-061). Informed consent and all procedures performed in this study were in accordance with the Declaration of 1964 Helsinki and the Ethical Guidelines for Medical and Health Research involving Human Subjects by the Ministry of Health, Labour and Welfare, the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Economy, Trade and Industry of Japan.Consent Written informed consent was obtained from the patient for publication of this research.",
  "authors": [
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Jun Masuda"
    },
    {
      "affiliations": [
        "National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan"
      ],
      "name": "Kazuma Kiyotani"
    },
    {
      "affiliations": [
        "NEC Corporation, Tokyo, Japan"
      ],
      "name": "Kazuhide Onoguchi"
    },
    {
      "affiliations": [
        "NEC OncoImmunity AS, Oslo, Norway"
      ],
      "name": "Per Brattås"
    },
    {
      "affiliations": [
        "NEC OncoImmunity AS, Oslo, Norway"
      ],
      "name": "Hugues Fontenelle"
    },
    {
      "affiliations": [
        "NEC OncoImmunity AS, Oslo, Norway"
      ],
      "name": "Angelina Sverchkova"
    },
    {
      "affiliations": [
        "NEC OncoImmunity AS, Oslo, Norway"
      ],
      "name": "Sumana Kalyanasundaram"
    },
    {
      "affiliations": [
        "NEC Laboratories Europe GmbH, Heidelberg, Germany"
      ],
      "name": "Pierre Machart"
    },
    {
      "affiliations": [
        "NEC Corporation, Tokyo, Japan"
      ],
      "name": "Yuki Tanaka"
    },
    {
      "affiliations": [
        "NEC Corporation, Tokyo, Japan"
      ],
      "name": "Daiki Miura"
    },
    {
      "affiliations": [
        "NEC Corporation, Tokyo, Japan"
      ],
      "name": "Noboru Nagata"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Koji Yoshino"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Mingyon Mun"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Yasuji Miyakita"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Hiroki Mitani"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Souya Nunobe"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Yu Takahashi"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Hiroyuki Kanao"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Takashi Akiyoshi"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Keisuke Ae"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Kengo Takeuchi"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Junji Yonese"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Masayuki Watanabe"
    },
    {
      "affiliations": [
        "Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Seiichi Mori"
    },
    {
      "affiliations": [
        "Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan"
      ],
      "name": "Seiya Imoto"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Ippei Fukada"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Shunji Takahashi"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Takayuki Ueno"
    },
    {
      "affiliations": [
        "National Cancer Center Hospital, Tokyo, Japan"
      ],
      "name": "Noboru Yamamoto"
    },
    {
      "affiliations": [
        "NEC OncoImmunity AS, Oslo, Norway"
      ],
      "name": "Kaïdre Bendjama"
    },
    {
      "affiliations": [
        "The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"
      ],
      "name": "Shigehisa Kitano"
    }
  ],
  "title": "162 A whole-genome-informed pipeline for neoantigen discovery in solid tumors: integrating SNV, splice variant, and exon-transposon junction analysis to enable personalized cancer vaccines",
  "uid": "13d938b8-983c-5a3c-ac38-22dd0de36661"
}