{
  "abstract": "The dense glycocalyx of cancer cells can restrict immune-cell access to surface antigens and limit CAR-T cell activity. Here, we show that mucin density and epitope position determine how glycocalyx remodeling affects CAR-T cell recognition and killing. We identify KLK5 as a human protease that cleaves tumor-associated mucins, increases access to membrane-proximal antigens, and enhances CAR-T cell function. We then engineer CAR-T cells to display or secrete KLK5, enabling remodeling of the tumor glycocalyx during antigen recognition. KLK5-engineered CAR-T cells improved tumor control across multiple xenograft models, and KLK5-secreting MUC17 CAR-T cells produced the strongest in vivo benefit, prolonging survival compared with conventional MUC17 CAR-T cells. These findings show that CAR-T cells can be engineered to breach the mucin-rich glycocalyx while preserving accessible target epitopes.",
  "abstract_shown": true,
  "affiliations": [
    "Massachusetts General Hospital and Harvard Medical School"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "S. Park"
    },
    {
      "name": "C. Ho"
    },
    {
      "name": "A. N. Wolff"
    },
    {
      "name": "Y. Fan"
    },
    {
      "name": "A. A. Bouffard"
    },
    {
      "name": "J. Paek"
    },
    {
      "name": "A. Mucci"
    },
    {
      "name": "T. R. Berger"
    },
    {
      "name": "M. J. Paszek"
    },
    {
      "name": "M. V. Maus"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e924w89vbkg20.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754490",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754490v1.full",
  "id": "e924w89vbkg20",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754490v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioengineering"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7214647713",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754490v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e924w89vbkg20.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:44Z",
      "native_id": "10.64898/2026.09.25.754490",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754490v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx",
  "title_text": "Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:44Z",
  "url": "https://research.draconitic.com/paper/e924w89vbkg20",
  "venue": "bioRxiv",
  "versions": []
}