A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients
Open accessAbstract
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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A24 induced apoptosis and blocked ex vivo proliferation of malignant T cells from both chronic and acutely infected patients.
“A pre-clinical study characterised the potential of A24, which induced apoptosis and blocked ex vivo proliferation of malignant T cells from both chronic and acutely infected patients [207].”
From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [207]
The section on ex vivo proliferation reports that A24 significantly inhibited cells from patients with both acute and chronic ATL. The apoptosis section reports apoptosis in tumor cells from acute ATL patients and in a nonacute cell-line model, but does not establish apoptosis in cells from chronic ATL patients. The paper describes acute and chronic forms of ATL, not acute versus chronic infection. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAnti-TfR treatment was only effective in some cancers such as adult T-cell leukemia/lymphoma (ATL) and leukemia.
“However, treatment was only effective in some cancers such as adult T-cell leukemia/lymphoma (ATL) and leukemia [99,100].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [100]
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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
- 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
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › 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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