Cited by 114T-cell and Retrovirus StudiesMonoclonal and Polyclonal Antibodies ResearchT-cell and B-cell Immunology

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A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients

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Moura, I. C.·2004·Blood

DOI 10.1182/blood-2003-07-2440

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Abstract

Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoid proliferative disease that exists under diverse clinical forms ranging from chronic to acute. Although leukemic cells from patients with ATL exhibit an intrinsic resistance to chemotherapy, monoclonal antibodies directed against CD25 (interleukin 2 receptor alpha [IL-2Ralpha] antibody) have been used as specific therapeutic agents. However, significant clinical results with these antibodies have been demonstrated only in chronic forms of ATL. In contrast to resting T cells, human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells constitutively express high levels of surface transferrin receptor (TfR). Herein, we report the characterization of a new monoclonal antibody (mAb A24) directed against the human TfR and the evaluation of its capacity to block the proliferation of ATL cells ex vivo. We determined that A24 binds TfR with an equilibrium constant (K'd) of 2.7 nM and competes with transferrin for binding to TfR. A24 also inhibited [55Fe]-transferrin uptake in activated T cells and blocked T-cell proliferation. Moreover, A24 reduced and impaired TfR expression and recycling, respectively. Most important, we showed that A24 blocked the ex vivo proliferation of malignant T cells from both acute and chronic forms of ATL, through induction of programmed cell death. Therefore efficient therapeutic tools to treat acute forms of ATL might be derived from A24.

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Authors: Moura, I. C.
Affiliations: Inserm (FR)
Corresponding author: Moura, I. C.
ORCID: Moura, I. C.
Venue: Blood
Publisher: American Society of Hematology
Published: 2004-03-01
Volume: 103
Issue: 5
Pages: 1838-1845
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2003-07-2440
OpenAlex: W2039030099
Cited by: 114
References: 46
Citations by year: 2026: 2 · 2025: 1 · 2024: 8 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 9 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 5
FWCI: 2.31
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Funders: Ligue Contre le Cancer
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: adult T-cell leukemia/lymphoma, transferrin receptor, apoptosis, T cell proliferation inhibition, HTLV-1, transferrin uptake, receptor recycling, targeted therapy
MeSH terms: Antibodies, Monoclonal, Cell Division, Dose-Response Relationship, Drug, Flow Cytometry, Humans, Iron, Kinetics, Leukocytes, Mononuclear, Lymphocyte Activation, Protein Binding, Receptors, Transferrin, T-Lymphocytes, Transferrin, Human T-lymphotropic virus 1, Receptors, Interleukin-2, Leukemia, T-Cell, Cell Death, Apoptosis, Microscopy, Confocal, Surface Plasmon Resonance

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A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients

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