{
  "abstract": "AXL is a membrane-accessible receptor tyrosine kinase and a potential antibody–drug conjugate (ADC) target, but its therapeutic relevance in soft-tissue sarcoma remains incompletely defined. We evaluated the AXL-directed pyrrolobenzodiazepine ADC ADCT-601/mipasetamab uzoptirine using a sarcoma tissue microarray, patient-derived cell lines, and patient-derived xenografts. AXL expression was broad but heterogeneous, with the highest histotype-level expression in myxofibrosarcoma and undifferentiated pleomorphic sarcoma. In the patient-linked tissue-microarray cohort, AXL H-score was not associated with metastasis-free or overall survival after clinicopathologic adjustment. ADCT-601 was substantially more potent than a non-targeting anti-gp120 control ADC carrying the same SG3199-containing payload. Free-payload sensitivity varied between cell lines, indicating that intrinsic payload susceptibility contributes to activity, while the payload-matched comparison supports an additional effect of AXL-mediated delivery. ADCT-601 induced cell-cycle perturbation, apoptosis, and γ-H2AX accumulation. Combination experiments identified enhanced activity with DNA damage-response inhibition, particularly ATR inhibition, and in vivo studies supported antitumor activity in two sarcoma xenograft models. These data support biomarker-enriched development of next-generation AXL-directed ADC strategies while emphasizing antigen heterogeneity and therapeutic-index optimization.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Nathan El-Ghazzi"
    },
    {
      "name": "Tony Sourisseau"
    },
    {
      "name": "Vanessa Chaire"
    },
    {
      "name": "Tom del Ben"
    },
    {
      "name": "Marie-Alix Derieppe"
    },
    {
      "name": "Lucile Vanhersecke"
    },
    {
      "name": "Christophe Rey"
    },
    {
      "name": "Alban Bessede"
    },
    {
      "name": "Jean-Max Pasquet"
    },
    {
      "name": "Antoine Italiano"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/awkqsgdagj7y8.bib",
  "cited_by": 0,
  "doi": "10.1186/s13045-026-01851-1",
  "fulltext_url": null,
  "id": "awkqsgdagj7y8",
  "issns": [
    "1756-8722"
  ],
  "landing_url": "https://hal.science/hal-05805095v1",
  "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/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.can"
    ],
    [
      "hal",
      "1.sdv.sp"
    ],
    [
      "hal",
      "2.sdv.sp.pharma"
    ],
    [
      "openalex",
      "2740|Sarcoma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7222618238",
  "pdf_url": "https://hal.science/hal-05805095/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": "BioMed Central",
  "ris": "https://research.draconitic.com/paper/awkqsgdagj7y8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:59Z",
      "native_id": "hal-05805095",
      "source": "hal",
      "url": "https://hal.science/hal-05805095v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.can",
      "subfield": "oncology"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.sp",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "AXL-directed antibody–drug conjugate therapy in soft-tissue sarcoma",
  "title_text": "AXL-directed antibody–drug conjugate therapy in soft-tissue sarcoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:59Z",
  "url": "https://research.draconitic.com/paper/awkqsgdagj7y8",
  "venue": "Journal of Hematology and Oncology",
  "versions": []
}