{
  "abstract": "Artificial intelligence (AI) methods for proteins have advanced rapidly, improving structure prediction and design, particularly for de novo binders. However, most evaluations emphasize binding affinity rather than higher-order biological function. We present Bits to Binders , a global competition evaluating de novo binder design in the context of chimeric antigen receptor (CAR) T cells. Teams from 42 countries submitted 12,000 designs of 80-amino acid de novo minibinders targeting human CD20 as CAR binding domains. Designs were screened by pooled CAR-T proliferation, identifying 707 designs exhibiting significant CD20-specific enrichment, with team hit rates from 0.6% to 38.4%. Top-performing candidates were validated as individual constructs, measuring CD20-specific proliferation, expansion, cytokine production, and targeted cell lysis. We identified common design methodologies and factors correlated with DNA synthesis, expression, and target-specific T cell activation which nearly double the success rates when applied as a retrospective filter. We release this dataset as an open resource, with practical recommendations to support more effective AI-driven binder design.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA",
    "The BioML Society, Austin, TX, USA",
    "LifEngine Animal Health (LEAH) Laboratories Incorporated, Minneapolis, MN, USA",
    "Department of Materials, Imperial College London, London, United Kingdom",
    "University of Texas at Austin, Austin, TX, USA",
    "Imperial College London, London, UK",
    "Monash University, Melbourne, VIC, Australia",
    "University of Toronto, Toronto, ON, Canada",
    "Institute for Drug Discovery, Leipzig University, Leipzig, Germany",
    "EPFL, Lausanne, Switzerland",
    "University of Oldenburg, Oldenburg, Germany",
    "Stockholm University, Stockholm, Sweden",
    "Czech Technical University in Prague, Prague, Czechia",
    "University of California San Diego, San Diego, CA, USA",
    "University of Oxford, Oxford, UK",
    "University of Texas Southwestern Medical Center, Dallas, TX, USA",
    "Virtue Therapeutics, Gurugram, India",
    "University of Illinois Urbana-Champaign, Champaign, IL, USA",
    "McGill University, Montreal, QC, Canada",
    "Sungkyunkwan University, Suwon, South Korea",
    "Vanderbilt University, Nashville, TN, USA",
    "Uppsala University, Uppsala, Sweden",
    "Gensaic, Cambridge, MA, USA",
    "Hebrew University of Jerusalem, Jerusalem, Israel",
    "University of Florida, Gainesville, FL, USA",
    "University of Washington, Seattle, WA, USA",
    "Purdue University, West Lafayette, IN, USA",
    "University of Tehran, Tehran, Iran",
    "Taras Shevchenko National University of Kyiv, Kyiv, Ukraine",
    "Myriad Genetics, Salt Lake City, UT, USA",
    "Harvard University, Cambridge, MA, USA",
    "Aibio AB, Klagshamn, Sweden",
    "Boltzmann Labs, Hyderabad, India",
    "National Institute of Chemistry, Ljubljana, Slovenia",
    "Seoul National University, Seoul, South Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 100,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Clayton W. Kosonocky",
      "orcid": "0000-0002-6420-8615"
    },
    {
      "affs": [
        2
      ],
      "name": "Alex M. Abel",
      "orcid": "0000-0003-4022-2495"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Aaron L. Feller",
      "orcid": "0000-0002-4476-1026"
    },
    {
      "affs": [
        2
      ],
      "name": "Amanda Cifuentes Rieffer"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Phillip R. Woolley",
      "orcid": "0000-0003-4473-9424"
    },
    {
      "affs": [
        3
      ],
      "name": "Jakub Lála",
      "orcid": "0000-0002-5424-5260"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Delbert S. Barth",
      "orcid": "0000-0003-3690-3909"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tynan Gardner"
    },
    {
      "name": "Bits to Binders Competitors"
    },
    {
      "affs": [
        4
      ],
      "name": "Daniel Acosta"
    },
    {
      "affs": [
        5
      ],
      "name": "Stefano Angioletti‐Uberti",
      "orcid": "0000-0003-2917-2415"
    },
    {
      "affs": [
        6
      ],
      "name": "Vinayak Annapure"
    },
    {
      "name": "Neil Anthony"
    },
    {
      "affs": [
        7
      ],
      "name": "Rana A Barghout"
    },
    {
      "affs": [
        8
      ],
      "name": "Max Beining",
      "orcid": "0009-0007-9513-822X"
    },
    {
      "affs": [
        9
      ],
      "name": "Parth Bibekar",
      "orcid": "0000-0002-7767-4447"
    },
    {
      "affs": [
        10
      ],
      "name": "Dionessa Biton"
    },
    {
      "affs": [
        11
      ],
      "name": "Patrick Bryant",
      "orcid": "0000-0003-3439-1866"
    },
    {
      "affs": [
        12
      ],
      "name": "Anton Bushuiev",
      "orcid": "0009-0007-4783-6584"
    },
    {
      "affs": [
        13
      ],
      "name": "Cianna N. Calia",
      "orcid": "0000-0002-6171-319X"
    },
    {
      "affs": [
        14
      ],
      "name": "Ava Chan",
      "orcid": "0000-0001-9801-4563"
    },
    {
      "affs": [
        15
      ],
      "name": "Jie Chen",
      "orcid": "0000-0003-2151-5276"
    },
    {
      "affs": [
        16
      ],
      "name": "Akshay Chenna",
      "orcid": "0000-0001-6830-3751"
    },
    {
      "affs": [
        17
      ],
      "name": "Nicole Chiang",
      "orcid": "0009-0005-9329-0434"
    },
    {
      "affs": [
        7
      ],
      "name": "Vivian Chu"
    },
    {
      "affs": [
        17
      ],
      "name": "Joseph Clark"
    },
    {
      "affs": [
        4
      ],
      "name": "Alia Clark‐ElSayed",
      "orcid": "0000-0001-9602-4231"
    },
    {
      "affs": [
        18
      ],
      "name": "Elliot Cole"
    },
    {
      "affs": [
        15
      ],
      "name": "Qian Cong",
      "orcid": "0000-0002-8909-0414"
    },
    {
      "affs": [
        19
      ],
      "name": "Shreyasi Das"
    },
    {
      "affs": [
        17
      ],
      "name": "Tanner Dean"
    },
    {
      "affs": [
        20
      ],
      "name": "Tyler Derr",
      "orcid": "0000-0002-0080-5998"
    },
    {
      "affs": [
        21
      ],
      "name": "Alejandro Diaz"
    },
    {
      "affs": [
        15
      ],
      "name": "Jesse Durham",
      "orcid": "0000-0001-6335-1332"
    },
    {
      "affs": [
        8
      ],
      "name": "Moritz Ertelt",
      "orcid": "0009-0004-2506-6660"
    },
    {
      "affs": [
        22
      ],
      "name": "Antonio Fonseca"
    },
    {
      "affs": [
        23
      ],
      "name": "Ora Schueler‐Furman",
      "orcid": "0000-0002-1624-0362"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tynan Gardner"
    },
    {
      "affs": [
        24
      ],
      "name": "Jokent T. Gaza",
      "orcid": "0000-0002-7836-4539"
    },
    {
      "affs": [
        25
      ],
      "name": "Nathaniel Greenwood"
    },
    {
      "affs": [
        15
      ],
      "name": "Rui Guo"
    },
    {
      "affs": [
        26
      ],
      "name": "Abel Gurung",
      "orcid": "0009-0008-7282-9252"
    },
    {
      "affs": [
        8
      ],
      "name": "Vivian Haas",
      "orcid": "0000-0002-7047-5517"
    },
    {
      "affs": [
        27
      ],
      "name": "Seyed Alireza Hashemi"
    },
    {
      "affs": [
        8
      ],
      "name": "Dieter Hoffmann"
    },
    {
      "affs": [
        28
      ],
      "name": "Sofiia Hoian"
    },
    {
      "affs": [
        29
      ],
      "name": "Corey Howe"
    },
    {
      "affs": [
        30
      ],
      "name": "Calvin XiaoYang Hu"
    },
    {
      "affs": [
        31
      ],
      "name": "Jinling Huang"
    },
    {
      "affs": [
        21
      ],
      "name": "Nader Ibrahim"
    },
    {
      "affs": [
        4
      ],
      "name": "Satoshi Ishida"
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    {
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        19
      ],
      "name": "Ansar Ahmad Javed"
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    {
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        32
      ],
      "name": "Aswini Javvadi"
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    {
      "affs": [
        33
      ],
      "name": "Roman Jerala",
      "orcid": "0000-0002-6337-5251"
    },
    {
      "affs": [
        32
      ],
      "name": "Daksh Joshi"
    },
    {
      "name": "Even Kiely"
    },
    {
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        34
      ],
      "name": "Haelyn Kim",
      "orcid": "0009-0004-6369-0181"
    },
    {
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        17
      ],
      "name": "Diego Kleiman"
    },
    {
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        23
      ],
      "name": "Sarah Knapp"
    },
    {
      "affs": [
        6
      ],
      "name": "Huan Koh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ebspsxdgnby5k.bib",
  "cited_by": 12,
  "doi": "10.1038/s44320-026-00246-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728253/",
  "id": "ebspsxdgnby5k",
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    "1744-4292"
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  "landing_url": "https://link.springer.com/10.1038/s44320-026-00246-1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
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      "heading",
      "Article"
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      "2730|CAR-T cell therapy research"
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  "pdf_url": "https://link.springer.com/content/pdf/10.1038/s44320-026-00246-1.pdf",
  "pmcid": "PMC13001334",
  "pmid": "41867703",
  "published": "2026-10-08",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/ebspsxdgnby5k.ris",
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  "subjects": [
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      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
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  ],
  "title": "Validation and analysis of 12,000 AI-driven CAR-T designs in the Bits to Binders competition",
  "title_text": "Validation and analysis of 12,000 AI-driven CAR-T designs in the Bits to Binders competition",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:39Z",
  "url": "https://research.draconitic.com/paper/ebspsxdgnby5k",
  "venue": "Molecular Systems Biology",
  "versions": []
}