{
  "abstract": "Personalized antigen-directed immunotherapies, including personalized cancer vaccines, are emerging as promising therapeutic modalities for a range of cancer types. Immune monitoring can be used to evaluate the efficacy of a vaccine in stimulating the immune response pre- and post-vaccination; however, such approaches typically stop short of identifying which T cell receptors (TCRs) are functionally driving therapeutic responses. Here, we present a case report of immune monitoring and subsequent TCR discovery experiments following administration of personalized cancer vaccines in a patient with locally recurrent osteosarcoma. Whole PBMCs were stimulated with vaccine peptides (>16 AA) in vitro for 11 days, after which IFN{gamma} ELISPOT identified total T cell responses for 12 of 15 tested peptides post-vaccination. In vitro expanded samples were submitted for 10x single-cell TCR sequencing, from which 26 TCRs were chosen for generation of TCR-T cells based on clonal expansion and culture specificity. Of the generated TCR-T cells, 25 produced functional TCRs, 4 of which were specific to vaccine peptides. However, downstream testing revealed each was MHC class-II restricted. To address this, we repeated the in vitro stimulations with co-cultures of isolated CD8+ T cells with autologous dendritic cells, and cultures of whole PBMCs with anti-MHC class-II blocking antibody. These cultures yielded 10 additional TCRs, 2 of which were responsive to a vaccine peptide containing a MAP2 frameshift mutation. These findings demonstrate an effective approach for leveraging post-vaccination expanded antigen-specific T cell populations for discovery of novel T cell receptors for downstream cellular therapies.",
  "abstract_shown": true,
  "affiliations": [
    "The University of North Carolina at Chapel Hill"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "S. N. Bennett"
    },
    {
      "name": "J. Alley"
    },
    {
      "name": "M. Shabrang"
    },
    {
      "name": "J. Garness"
    },
    {
      "name": "K. McKinnon"
    },
    {
      "name": "A. Smith"
    },
    {
      "name": "W. B. Inabinett"
    },
    {
      "name": "W. A. Hoos"
    },
    {
      "name": "M. A. Thompson"
    },
    {
      "name": "A. N. Rubinsteyn"
    },
    {
      "affs": [
        0
      ],
      "name": "B. G. Vincent"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7fpqv99169g8q.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.757920",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757920v1.full",
  "id": "7fpqv99169g8q",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757920v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7221890169",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757920v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7fpqv99169g8q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:00Z",
      "native_id": "10.64898/2026.10.09.757920",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757920v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Discovery of frameshift-associated TCRs following personalized neoantigen vaccination in a patient with osteosarcoma",
  "title_text": "Discovery of frameshift-associated TCRs following personalized neoantigen vaccination in a patient with osteosarcoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:00Z",
  "url": "https://research.draconitic.com/paper/7fpqv99169g8q",
  "venue": "bioRxiv",
  "versions": []
}