{
  "abstract": "Background: Chronic lymphocytic leukemia (CLL) is characterized by T-cell dysfunction that limits the efficacy of immunotherapies, including CD20×CD3 bispecific antibodies. Protein tyrosine phosphatases non-receptor type 2/1 PTPN2/PTPN1 are central intracellular negative regulators of T-cell activation. Preclinical studies show that deletion or PTPN2/PTPN1 inhibition increased T-cell activation, proliferation, and antitumor activity. This study aimed to investigate the potential of PTPN2/PTPN1 inhibition in combination with the bispecific antibody mosunetuzumab as a therapeutic approach for CLL.\n\nMethods: Peripheral blood mononuclear cells (PBMCs) obtained from CLL patients were used in all experiments. The effects of PTPN2/PTPN1 inhibition in combination with mosunetuzumab, were evaluated using flow cytometry, confocal microscopy, ELISA, and Incucyte Live-Cell Analysis to assess T-cell activation, immune synapse formation and cytotoxic activity.\n\nResults: Pretreatment with the PTPN2/PTPN1 inhibitor ABBV-CLS-484 (AC484) enhanced T-cell activation following CD3/CD28 stimulation, as demonstrated by increased expression of the activation markers CD69 and CD25. Confocal microscopy revealed increased CD8+ T-cell size, enhanced granzyme B expression and release, and more robust immune synapse formation following treatment with mosunetuzumab +/-AC484. Incucyte imaging of CLL-T-cell co-cultures demonstrated enhanced T-cell proliferation, increased CLL-T-cell clustering, and a modest increase in cytotoxicity with the combination of AC484 and mosunetuzumab. Consistent with these findings, ELISA assays showed increased secretion of granzyme B and IFN-γ.\n\nConclusion: Combining the PTPN2/PTPN1 inhibitor AC484 with mosunetuzumab enhanced T-cell activation, proliferation, granzyme B and IFN-γ secretion, and anti-CLL cytotoxicity in CLL samples, supporting further evaluation of PTPN2/PTPN1 inhibition as a strategy to enhance the efficacy of CLL immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hematology, Tel Aviv Sourasky University Medical Center (Ichilov)",
    "Gray Faculty of Medicine and Health Sciences, Tel Aviv University"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Liron Yitzhak"
    },
    {
      "affs": [
        0
      ],
      "name": "Yamit Shorer Arbel"
    },
    {
      "affs": [
        0
      ],
      "name": "Yotam Bronstein"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ben-Zion Katz"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yair Herishanu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6bee6ezbhdfcb.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1948967",
  "fulltext_url": "https://europepmc.org/articles/PMC13687270",
  "id": "6bee6ezbhdfcb",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1948967/full",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2716|Chronic Lymphocytic Leukemia Research"
    ]
  ],
  "openalex": "W7221038171",
  "pdf_url": "https://europepmc.org/articles/PMC13687270?pdf=render",
  "pmcid": "PMC13687270",
  "pmid": "42922970",
  "published": "2026-10-08",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6bee6ezbhdfcb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1948967",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1948967/full"
    },
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42922970",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42922970"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Chronic Lymphocytic Leukemia Research",
      "subfield": "human-genetics"
    }
  ],
  "title": "PTPN2/PTPN1 inhibition enhances ex vivo T- cell responses and potentiates mosunetuzumab activity in chronic lymphocytic leukemia",
  "title_text": "PTPN2/PTPN1 inhibition enhances ex vivo T- cell responses and potentiates mosunetuzumab activity in chronic lymphocytic leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/6bee6ezbhdfcb",
  "venue": "Frontiers in Immunology",
  "versions": []
}