ArticleJournal of hematology & oncology2017
Targeting the CXCR4 pathway using a novel anti-CXCR4 IgG1 antibody (PF-06747143) in chronic lymphocytic leukemia.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- STAT3 as a Candidate Shared Regulator of the CXCR4/CXCL12 and CXCR5/CXCL13 Homing Axes in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2026Review
- The Fibro-Immune Landscape Across Organs: A Single-Cell Comparative Study of Human Fibrotic Diseases.International journal of molecular sciences · 2026Article
- Anti-myeloma activity of the CXCR4 antagonist WZ811.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Functional differences between CLL- and ALL-derived CAR T cells in a 3D tumor microenvironment highlight CXCR4 and IL-10 as potential modulatory targets.HemaSphere · 2025Article
- Targeting the chemokine receptor CXCR4 for cancer therapies.Biomarker research · 2025Review
- Artificial blood-hope and the challenges to combat tumor hypoxia for anti-cancer therapy.Medical & biological engineering & computing · 2025Review
- Tumor microenvironment as a novel therapeutic target for lymphoid leukemias.Annals of hematology · 2025Review
- Structural insights into CXCR4 modulation and oligomerization.Nature structural & molecular biology · 2025Article
- Proliferating CLL cells express high levels of CXCR4 and CD5.HemaSphere · 2024Article
- Tuning the B-CLL microenvironment: evidence for BAG3 protein- mediated regulation of stromal fibroblasts activity.Cell death discovery · 2024Article
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.Journal of cancer research and clinical oncology · 2023Review
- CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.International journal of biological sciences · 2023Review
- The protective role of the microenvironment in hairy cell leukemia treatment: Facts and perspectives.Frontiers in oncology · 2023Review
- Emerging role of chemokines in small cell lung cancer: Road signs for metastasis, heterogeneity, and immune response.Seminars in cancer biology · 2022Review
- Recent Advances in CXCL12/CXCR4 Antagonists and Nano-Based Drug Delivery Systems for Cancer Therapy.Pharmaceutics · 2022Review
- Article
- Targeting the tumor microenvironment in chronic lymphocytic leukemia.Haematologica · 2021Review
- Impact of Immune Parameters and Immune Dysfunctions on the Prognosis of Patients with Chronic Lymphocytic Leukemia.Cancers · 2021Review
- At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer.Journal of leukocyte biology · 2021Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow. Therefore, we hypothesized that targeting CXCR4 with an IgG1 antibody, PF-06747143, may constitute an effective therapeutic approach for CLL.
methodsPatient-derived primary CLL-B cells were assessed for cytotoxicity in an in vitro model of CLL microenvironment. PF-06747143 was analyzed for cell death induction and for its potential to interfere with the chemokine CXCL12-induced mechanisms, including migration and F-actin polymerization. PF-06747143 in vivo efficacy was determined in a CLL murine xenograft tumor model.
resultsPF-06747143, a novel-humanized IgG1 CXCR4 antagonist antibody, induced cell death of patient-derived primary CLL-B cells, in presence or absence of stromal cells. Moreover, cell death induction by the antibody was independent of CLL high-risk prognostic markers. The cell death mechanism was dependent on CXCR4 expression, required antibody bivalency, involved reactive oxygen species production, and did not require caspase activation, all characteristics reminiscent of programmed cell death (PCD). PF-06747143 also induced potent B-CLL cytotoxicity via Fc-driven antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity activity (CDC). PF-06747143 had significant combinatorial effect with standard of care (SOC) agents in B-CLL treatment, including rituximab, fludarabine (F-ara-A), ibrutinib, and bendamustine. In a CLL xenograft model, PF-06747143 decreased tumor burden and improved survival as a monotherapy, and in combination with bendamustine.
conclusionsWe show evidence that PF-06747143 has biological activity in CLL primary cells, supporting a rationale for evaluation of PF-06747143 for the treatment of CLL patients.
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