{
  "abstract": "Cytokines can elicit potent antitumor immunity, but their clinical use is often limited by systemic immune activation and dose-limiting toxicity. Protease-responsive masking offers a way to improve selectivity by linking cytokine activity to disease-associated protease cleavage, but current approaches have faced several challenges. Here we describe a de novo protein design strategy for generating protease-activatable cytokine prodrugs that overcomes these challenges. We use this strategy to design and characterize cytokine prodrugs and well-behaved AND-gated split systems that require both target-dependent colocalization and proteolytic unmasking to generate active cytokines. In challenging syngeneic tumor models, our IL-21 prodrugs reduced treatment-associated toxicity while maintaining antitumor efficacy.",
  "abstract_shown": true,
  "affiliations": [
    "University of Washington"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "H. Shin"
    },
    {
      "name": "J. G. Tello"
    },
    {
      "name": "C. J. Kim"
    },
    {
      "name": "J.-H. Chun"
    },
    {
      "name": "F. Peprah"
    },
    {
      "name": "B. D. Parent"
    },
    {
      "name": "T. Atajanova"
    },
    {
      "name": "R. A. I. Mahmud"
    },
    {
      "name": "L. Qiang"
    },
    {
      "name": "A. J. Aguirre"
    },
    {
      "name": "S. K. Dougan"
    },
    {
      "name": "M. Dougan"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Baker"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/44h8yg0hw2ryp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.19.752834",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752834v1.full",
  "id": "44h8yg0hw2ryp",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752834v1",
  "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",
      "bioengineering"
    ],
    [
      "openalex",
      "2741|Monoclonal and Polyclonal Antibodies Research"
    ]
  ],
  "openalex": "W7214276776",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752834v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/44h8yg0hw2ryp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:47Z",
      "native_id": "10.64898/2026.09.19.752834",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752834v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "De novo design of protease-activatable cytokine prodrugs",
  "title_text": "De novo design of protease-activatable cytokine prodrugs",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:47Z",
  "url": "https://research.draconitic.com/paper/44h8yg0hw2ryp",
  "venue": "bioRxiv",
  "versions": []
}