Skip to Main content Skip to Navigation
Journal articles

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

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 ␣ [IL-2R␣] 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 [ 55 Fe]-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.
Document type :
Journal articles
Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-03525664
Contributor : Patrick ENGLAND Connect in order to contact the contributor
Submitted on : Friday, January 14, 2022 - 6:06:40 AM
Last modification on : Saturday, January 22, 2022 - 3:35:05 AM
Long-term archiving on: : Friday, April 15, 2022 - 6:15:58 PM

File

article Moura et al 2004.pdf
Publisher files allowed on an open archive

Licence

Copyright

Identifiers

Collections

Citation

Ivan C. Moura, Yves Lepelletier, Bertrand Arnulf, Ali Bazarbachi, Renato C. Monteiro, et al.. A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients. Blood, American Society of Hematology, 2004, 103 (5), pp.1838 - 1845. ⟨10.1182/blood-2003-07-2440⟩. ⟨pasteur-03525664⟩

Share

Metrics

Record views

6

Files downloads

46