{
  "abstract": "TROP2 is expressed in many epithelial tumors including breast and lung cancers. It is a clinically validated ADC target based on approvals of sacituzumab govitecan for triple-negative breast cancer and datopotamab deruxtecan for HR-positive, HER2-negative breast cancer. An alternative cytotoxic approach was previously tested with PF-06664178/RN927C, an anti-TROP2 ADC with an auristatin payload, which entered clinical studies but could not be dosed efficaciously due to dose-limiting toxicities including skin rash, mucosal inflammation, and neutropenia. TroptimAb-SL-MMAE was engineered using an optimized anti-TROP2 sacituzumab antibody sequence (TroptimAb) to address issues related to hydrophobicity, non-specific uptake, and ADC developability. Sacituzumab was re ₋ humanized and modified to enhance FcRn-mediated salvage which extended systemic half-life and potentially improving tumor distribution. Its affinity was avidity-tuned to preferentially bind cells with higher TROP2 expression to reduce on-target/off-tumor toxicity. An engineered cysteine in the Fc domain enabled generation of a homogeneous DAR2 ADC and shielded the linker-payload to reduce hydrophobicity and improve biophysical properties. Linker conjugation chemistry was also optimized to improve stability versus earlier cysteine-conjugated ADCs. We describe the preclinical profile of TroptimAb-SL-MMAE including its design, mechanism of action, anti-tumor activity, and pharmacokinetics.",
  "abstract_shown": true,
  "affiliations": [
    "Discovery Biologics, Merck & Co., Inc. , , ,",
    "Pharmacokinetics, Dynamics, Metabolism and Bioanalytics (PDMB), Merck & Co., Inc. , , ,",
    "Quantitative Bioscience, Merck & Co., Inc. , , ,",
    "Discovery Chemistry, Merck & Co., Inc. , , ,",
    "Non-clinical Drug Safety, Merck & Co., Inc. , , ,",
    "Discovery Oncology, Merck & Co., Inc. , , ,",
    "Data AI and Genome Science, Merck & Co., Inc. , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 47,
  "authors": [
    {
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        0
      ],
      "name": "Laurence Fayadat-Dilman"
    },
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        0
      ],
      "name": "Andrew B. Waight"
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        1
      ],
      "name": "Lauren Adams"
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        2
      ],
      "name": "Peyman Akbari"
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        2
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      "name": "Minilik Angagaw"
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        0
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      "name": "Jeanne Baker"
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        0
      ],
      "name": "Michelle Castor"
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        0
      ],
      "name": "Andy Chen"
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        0
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      "name": "Daoyang Chen"
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    {
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        0
      ],
      "name": "Ming-Tang Chen"
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    {
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        0
      ],
      "name": "Ellen Chien"
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    {
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        3
      ],
      "name": "Jill E. Chrencik"
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        4
      ],
      "name": "Darcey Clark"
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        3
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      "name": "James Dutko"
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        0
      ],
      "name": "Mehabaw Derebe"
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        1
      ],
      "name": "Alan Goggins"
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    {
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        4
      ],
      "name": "Thomas Griffiths"
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    {
      "affs": [
        3
      ],
      "name": "Mee Ra Heon"
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    {
      "affs": [
        2
      ],
      "name": "Marlene C. Hinton"
    },
    {
      "affs": [
        1
      ],
      "name": "SuChun Hsieh"
    },
    {
      "affs": [
        0
      ],
      "name": "Amy Hsu"
    },
    {
      "affs": [
        5
      ],
      "name": "Zhong L. Hua"
    },
    {
      "affs": [
        0
      ],
      "name": "Mark Ibrahim"
    },
    {
      "affs": [
        1
      ],
      "name": "Mengxuan Jia"
    },
    {
      "affs": [
        3
      ],
      "name": "Rebecca E. Johnson"
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    {
      "affs": [
        3
      ],
      "name": "Simon B. Lang"
    },
    {
      "affs": [
        2
      ],
      "name": "Su-Yang Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniel Malashock"
    },
    {
      "affs": [
        6
      ],
      "name": "Aleksandra Olow"
    },
    {
      "affs": [
        4
      ],
      "name": "Michael Oropallo"
    },
    {
      "affs": [
        3
      ],
      "name": "Andrea T. Partridge"
    },
    {
      "affs": [
        2
      ],
      "name": "Vin Penaflor"
    },
    {
      "affs": [
        0
      ],
      "name": "Elnaz Rasti Boroujeni"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhao Ren"
    },
    {
      "affs": [
        0
      ],
      "name": "Karthik Sathiyamoorthy"
    },
    {
      "affs": [
        0
      ],
      "name": "Makiko Uchida"
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    {
      "affs": [
        1
      ],
      "name": "Derek Wiswell"
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    {
      "affs": [
        5
      ],
      "name": "Jane Xia"
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    {
      "affs": [
        2
      ],
      "name": "Peng Yang"
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    {
      "affs": [
        2
      ],
      "name": "Jennifer Yearley"
    },
    {
      "affs": [
        0
      ],
      "name": "Sultan Yilmaz"
    },
    {
      "affs": [
        0
      ],
      "name": "Yao Yu"
    },
    {
      "affs": [
        3
      ],
      "name": "John A. Flygare"
    },
    {
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        0
      ],
      "name": "Bernhard H. Geierstanger"
    },
    {
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        1
      ],
      "name": "Jianzhong Wen"
    },
    {
      "affs": [
        3
      ],
      "name": "W. Michael Seganish"
    },
    {
      "affs": [
        5
      ],
      "name": "Edward P. Bowman"
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  "bibtex": "https://research.draconitic.com/paper/34qqcf835ahn2.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1915652",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662851/?tool=EBI",
  "id": "34qqcf835ahn2",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13662851",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2741|Monoclonal and Polyclonal Antibodies Research"
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  "openalex": "W7214943342",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662851/pdf/?tool=EBI",
  "pmcid": "PMC13662851",
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/34qqcf835ahn2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:20Z",
      "native_id": "PMC:PMC13662851",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13662851"
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      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1915652",
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      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1915652/full"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "imaging"
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  ],
  "title": "Multi-parameter optimization of a novel anti-TROP2 MMAE antibody-drug-conjugate for solid tumor therapy",
  "title_text": "Multi-parameter optimization of a novel anti-TROP2 MMAE antibody-drug-conjugate for solid tumor therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/34qqcf835ahn2",
  "venue": "Frontiers in oncology",
  "versions": []
}