{
  "abstract": "Introduction: Tumor heterogeneity and signaling redundancy limit the efficacy of monospecific antibody therapies in solid malignancies. Here we used our platform of glyco-humanized polyclonal antibodies (GH-pAb), to investigate whether targeting multiple tumor-associated antigens provides integrated anti-tumor activity.\n\nMethods: GH-pAb (hereinafter XON7) were generated by immunization of double-knockout pigs with human tumor cells. Antigen specificity of XON7 was assessed using a human proteome array and validated by ELISA. Anti-tumor mechanisms were evaluated in vitro on 2D or 3D-cultures. Efficacy was tested in vivo in cell or patient-derived xenograft (CDX, PDX), in chicken chorioallantoic membrane (CAM) model, and in orthotopic/metastatic triple negative breast cancer (TNBC) models.\n\nResults: XON7 demonstrated tumor-restricted binding across tissue microarrays without detectable staining in matched normal tissues. Mechanistically, XON7 induced potent cytotoxicity across a wide tumor panel through complement activation, apoptosis, and antibody-dependent cellular phagocytosis. Proteome profiling identified predominant reactivities against solute carrier family 3 member 2 (SLC3A2), annexin A2 (ANXA2), and cytoskeleton-associated protein 4 (CKAP4), all broadly expressed tumor-associated surface proteins. Immunodepletion experiments revealed that concurrent targeting of these three targets was required to maintain the full anti-proliferative activity of XON7, supporting a multitarget-dependent mechanism. XON7 also induced released of high-mobility group protein box 1 (HMGB1), a hallmark of immunogenic cell death. In vivo , XON7 inhibited tumor growth in CDX and PDX models, and markedly reduced metastatic dissemination in orthotopic and intravenous TNBC models. In a CAM model, XON7 synergized with PD-1 blockade, enhancing tumor control and promoting macrophage polarization toward a M1 phenotype.\n\nConclusion: By simultaneously engaging non-redundant tumor pathways and reshaping the tumor microenvironment, XON7 may overcome key resistance mechanisms of solid tumors.",
  "abstract_shown": true,
  "affiliations": [
    "Xenothera , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Carine Ciron"
    },
    {
      "affs": [
        0
      ],
      "name": "Ophélie Dauphouy"
    },
    {
      "affs": [
        0
      ],
      "name": "Pierre Morice"
    },
    {
      "affs": [
        0
      ],
      "name": "Pierre-Joseph Royer"
    },
    {
      "affs": [
        0
      ],
      "name": "Gwenaëlle Evanno"
    },
    {
      "affs": [
        0
      ],
      "name": "Juliette Rousse"
    },
    {
      "affs": [
        0
      ],
      "name": "Françoise Shneiker"
    },
    {
      "affs": [
        0
      ],
      "name": "Bernard Vanhove"
    },
    {
      "affs": [
        0
      ],
      "name": "Odile Duvaux"
    },
    {
      "affs": [
        0
      ],
      "name": "Firas Bassissi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d57vvwq76xn8v.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1947593",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690644/?tool=EBI",
  "id": "d57vvwq76xn8v",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13690644",
  "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"
    ]
  ],
  "openalex": "W7221151815",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690644/pdf/?tool=EBI",
  "pmcid": "PMC13690644",
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/d57vvwq76xn8v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:00Z",
      "native_id": "PMC:PMC13690644",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13690644"
    },
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1947593",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1947593/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "imaging"
    }
  ],
  "title": "Tumor-antigen-specific polyclonal antibodies suppress tumor growth and metastasis in heterogeneous solid tumors",
  "title_text": "Tumor-antigen-specific polyclonal antibodies suppress tumor growth and metastasis in heterogeneous solid tumors",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/d57vvwq76xn8v",
  "venue": "Frontiers in oncology",
  "versions": []
}