Human agonistic TRAIL receptor antibodies Mapatumumab and Lexatumumab induce apoptosis in malignant mesothelioma and act synergistically with cisplatin.

Détails

Ressource 1Télécharger: BIB_E30C6D3DCE22.P001.pdf (504.32 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_E30C6D3DCE22
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Human agonistic TRAIL receptor antibodies Mapatumumab and Lexatumumab induce apoptosis in malignant mesothelioma and act synergistically with cisplatin.
Périodique
Molecular Cancer
Auteur⸱e⸱s
Belyanskaya L.L., Marti T.M., Hopkins-Donaldson S., Kurtz S., Felley-Bosco E., Stahel R.A.
ISSN
1476-4598 (Electronic)
ISSN-L
1476-4598
Statut éditorial
Publié
Date de publication
2007
Volume
6
Pages
66
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Résumé
BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is associated with exposure to asbestos, and projections suggest that the yearly number of deaths in Western Europe due to MPM will increase until 2020. Despite progress in chemo- and in multimodality therapy, MPM remains a disease with a poor prognosis. Inducing apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or agonistic monoclonal antibodies which target TRAIL-receptor 1 (TRAIL-R1) or TRAIL-R2 has been thought to be a promising cancer therapy.
RESULTS: We have compared the sensitivity of 13 MPM cell lines or primary cultures to TRAIL and two fully human agonistic monoclonal antibodies directed to TRAIL-R1 (Mapatumumab) and TRAIL-R2 (Lexatumumab) and examined sensitization of the MPM cell lines to cisplatin-induced by the TRAIL-receptor antibodies. We found that sensitivity of MPM cells to TRAIL, Mapatumumab and Lexatumumab varies largely and is independent of TRAIL-receptor expression. TRAIL-R2 contributes more than TRAIL-R1 to death-receptor mediated apoptosis in MPM cells that express both receptors. The combination of cisplatin with Mapatumumab or Lexatumumab synergistically inhibited the cell growth and enhanced apoptotic death. Furthermore, pre-treatment with cisplatin followed by Mapatumumab or Lexatumumab resulted in significant higher cytotoxic effects as compared to the reverse sequence. Combination-induced cell growth inhibition was significantly abrogated by pre-treatment of the cells with the antioxidant N-acetylcysteine.
CONCLUSION: Our results suggest that the sequential administration of cisplatin followed by Mapatumumab or Lexatumumab deserves investigation in the treatment of patients with MPM.
Mots-clé
Antibodies, Monoclonal/pharmacology, Antineoplastic Agents/pharmacology, Apoptosis/drug effects, Cisplatin/pharmacology, Drug Synergism, Flow Cytometry, Humans, Immunoblotting, Jurkat Cells/drug effects, Jurkat Cells/metabolism, Mesothelioma/drug therapy, Mesothelioma/metabolism, Receptors, TNF-Related Apoptosis-Inducing Ligand/immunology, Receptors, Tumor Necrosis Factor/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/08/2014 13:45
Dernière modification de la notice
20/08/2019 16:06
Données d'usage