Exploration of the Lysis Mechanisms of Leukaemic Blasts by Chimaeric T-Cells
Joint Authors
Chaperot, Laurence
Biagi, Ettore
Plumas, Joël
Jacob, Marie Christine
Gallot, Géraldine
Agostoni, Valentina
Pizzitola, Irene
Vié, Henri
Laurin, David
Aspord, Caroline
Marin, Virna
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2009), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-04-28
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Adoptive transfer of specific cytotoxic T lymphocytes (CTL) and Cytokine Induced Killer Cells (CIK) following genetic engineering of T-cell receptor zeta hold promising perspective in immunotherapy.
In the present work we focused on the mechanisms of anti-tumor action of effectors transduced with an anti-CD19 chimaeric receptor in the context of B-lineage acute lymphoblastic leukemia (B-ALL).
Primary B-ALL blasts were efficiently killed by both z-CD19 CTL and z-CD19 CIK effectors.
The use of death receptor mediated apoptosis of target cells was excluded since agonists molecules of Fas and TRAIL-receptors failed to induce cell death.
Perforin/granzyme pathway was found to be the mechanism of chimaeric effectors mediated killing.
Indeed, cytolytic effector molecules perforin as well as granzymes were highly expressed by CTL and CIK.
CD19 specific stimulation of transduced effectors was associated with degranulation as attested by CD107 membrane expression and high IFN-γ and TNF-α release.
Moreover inhibitors of the perforin-based cytotoxic pathway, Ca2+-chelating agent EGTA and Concanamycin A, almost completely abrogated B-ALL blast killing.
In conclusion we show that the cytolysis response of z-CD19 chimaeric effectors is predominantly mediated via perforin/granzyme pathway and is independent of death receptors signaling in primary B-ALL.
American Psychological Association (APA)
Laurin, David& Marin, Virna& Biagi, Ettore& Pizzitola, Irene& Agostoni, Valentina& Gallot, Géraldine…[et al.]. 2010. Exploration of the Lysis Mechanisms of Leukaemic Blasts by Chimaeric T-Cells. BioMed Research International،Vol. 2010, no. 2010, pp.1-9.
https://search.emarefa.net/detail/BIM-988817
Modern Language Association (MLA)
Laurin, David…[et al.]. Exploration of the Lysis Mechanisms of Leukaemic Blasts by Chimaeric T-Cells. BioMed Research International No. 2010 (Dec. 2010), pp.1-9.
https://search.emarefa.net/detail/BIM-988817
American Medical Association (AMA)
Laurin, David& Marin, Virna& Biagi, Ettore& Pizzitola, Irene& Agostoni, Valentina& Gallot, Géraldine…[et al.]. Exploration of the Lysis Mechanisms of Leukaemic Blasts by Chimaeric T-Cells. BioMed Research International. 2010. Vol. 2010, no. 2010, pp.1-9.
https://search.emarefa.net/detail/BIM-988817
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-988817