{
  "abstract": "Membrane-associated proliferating cell nuclear antigen (mPCNA) is an attractive tumor-selective antigen for antibody-drug conjugate (ADC) development. We generated a chimeric IgG1 ADC, RC14-MMAE, to exploit three key properties of mPCNA that support its use as an efficient delivery platform. First, flow-cytometric and imaging analyses show abundant mPCNA surface expression on multiple tumor cell lines and in JIMT1 xenografts, providing accessible epitopes for binding. Second, comparative profiling against non-malignant counterparts and normal mouse tissues reveals minimal or undetectable mPCNA at the plasma membrane of healthy cells, indicating a sharp tumor-normal differential expected to limit off-tumor targeting and improve the therapeutic window. Third, live-cell internalization assays demonstrate that RC14 rapidly accumulates in LAMP1-positive lysosomes after engaging mPCNA, confirming efficient trafficking along the endolysosomal pathway required for protease-mediated cleavage of the valine-citrulline linker and release of monomethyl auristatin E (MMAE). Consistent with this target profile, RC14-MMAE exhibits potent antigen-dependent cytotoxicity in mPCNA-positive tumor models in NSG mice, favorable pharmacokinetics, sustained payload retention in serum, robust in vivo antitumor activity with limited overt toxicity, and a significantly increased fraction of F4/80⁺ tumor-infiltrating myeloid cells within dissociated tumors. These findings establish mPCNA as a functionally validated, tumor-selective internalizing target and support RC14-MMAE as a first-in-class mPCNA-directed ADC with broad translational potential.",
  "abstract_shown": true,
  "affiliations": [
    "The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.",
    "Institiute of Pathology, Barzilai University Medical Center, Ashkelon, Israel.",
    "llse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.",
    "Blood Cell Development and Host Defense Program, Research Institute at Fox Chase Cancer Center, Philadelphia, PA, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Muhammad Abu Ahmad"
    },
    {
      "affs": [
        0
      ],
      "name": "Nir Miriam Ungar-Malma"
    },
    {
      "affs": [
        0
      ],
      "name": "Alon Naumchik"
    },
    {
      "affs": [
        0
      ],
      "name": "Noy Machluf-Katz"
    },
    {
      "affs": [
        0
      ],
      "name": "Olga Radinsky"
    },
    {
      "affs": [
        0
      ],
      "name": "Sarah Adi Eisdorfer"
    },
    {
      "affs": [
        0
      ],
      "name": "Abedallh Gara"
    },
    {
      "affs": [
        0
      ],
      "name": "Yosef Istoyler"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Irit Alon"
    },
    {
      "affs": [
        2
      ],
      "name": "Daniel Sevilla-Sanchez"
    },
    {
      "affs": [
        3
      ],
      "name": "Kerry S Campbell"
    },
    {
      "affs": [
        0
      ],
      "name": "Bar Kaufman"
    },
    {
      "affs": [
        0
      ],
      "name": "Moshe Elkabets"
    },
    {
      "affs": [
        0
      ],
      "name": "Angel Porgador"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ewasd3vmk1szc.bib",
  "cited_by": 0,
  "doi": "10.1080/2162402x.2026.2740432",
  "fulltext_url": "https://europepmc.org/articles/PMC13671430",
  "id": "ewasd3vmk1szc",
  "issns": [
    "2162-4011",
    "2162-402X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42873150",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2741|Monoclonal and Polyclonal Antibodies Research"
    ]
  ],
  "openalex": "W7221824456",
  "pdf_url": "https://europepmc.org/articles/PMC13671430?pdf=render",
  "pmcid": "PMC13671430",
  "pmid": "42873150",
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ewasd3vmk1szc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42873150",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42873150"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "imaging"
    }
  ],
  "title": "Targeting tumor-selective membrane-associated PCNA enables selective antibody-drug conjugate therapy.",
  "title_text": "Targeting tumor-selective membrane-associated PCNA enables selective antibody-drug conjugate therapy.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/ewasd3vmk1szc",
  "venue": "Oncoimmunology",
  "versions": []
}