In Vitro and In Vivo Comparison of Lymphocytes Transduced with a Human CD16 or with a Chimeric Antigen Receptor Reveals Potential Off-Target Interactions due to the IgG2 CH2-CH3 CAR-Spacer
Joint Authors
Clémenceau, Béatrice
Valsesia-Wittmann, Sandrine
Jallas, Anne-Catherine
Vivien, Régine
Rousseau, Raphaël
Marabelle, Aurélien
Caux, Christophe
Vié, Henri
Source
Journal of Immunology Research
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-11-17
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
The present work was designed to compare two mechanisms of cellular recognition based on Ab specificity: firstly, when the anti-HER2 mAb trastuzumab bridges target cells and cytotoxic lymphocytes armed with a Fc receptor (ADCC) and, secondly, when HER2 positive target cells are directly recognized by cytotoxic lymphocytes armed with a chimeric antigen receptor (CAR).
To compare these two mechanisms, we used the same cellular effector (NK-92) and the same signaling domain (FcεRIγ).
The NK-92 cytotoxic cell line was transfected with either a FcγRIIIa-FcεRIγ (NK-92CD16) or a trastuzumab-based scFv-FcεRIγ chimeric receptor (NK-92CAR).
In vitro, the cytotoxic activity against HER2 positive target cells after indirect recognition by NK-92CD16 was always inferior to that observed after direct recognition by NK-92CAR.
In contrast, and somehow unexpectedly, in vivo, adoptive transfer of NK-92CD16 + trastuzumab but not of NK-92CAR induced tumor regression.
Analysis of the in vivo xenogeneic system suggested that the human CH2-CH3 IgG2 used as a spacer in our construct was able to interact with the FcR present at the cell surface of the few NSG-FcR+ remaining immune cells.
This interaction, leading to blockage of the NK-92CAR in the periphery of the engrafted tumor cells, stresses the critical role of the composition of the spacer domain.
American Psychological Association (APA)
Clémenceau, Béatrice& Valsesia-Wittmann, Sandrine& Jallas, Anne-Catherine& Vivien, Régine& Rousseau, Raphaël& Marabelle, Aurélien…[et al.]. 2015. In Vitro and In Vivo Comparison of Lymphocytes Transduced with a Human CD16 or with a Chimeric Antigen Receptor Reveals Potential Off-Target Interactions due to the IgG2 CH2-CH3 CAR-Spacer. Journal of Immunology Research،Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1068490
Modern Language Association (MLA)
Clémenceau, Béatrice…[et al.]. In Vitro and In Vivo Comparison of Lymphocytes Transduced with a Human CD16 or with a Chimeric Antigen Receptor Reveals Potential Off-Target Interactions due to the IgG2 CH2-CH3 CAR-Spacer. Journal of Immunology Research No. 2015 (2015), pp.1-13.
https://search.emarefa.net/detail/BIM-1068490
American Medical Association (AMA)
Clémenceau, Béatrice& Valsesia-Wittmann, Sandrine& Jallas, Anne-Catherine& Vivien, Régine& Rousseau, Raphaël& Marabelle, Aurélien…[et al.]. In Vitro and In Vivo Comparison of Lymphocytes Transduced with a Human CD16 or with a Chimeric Antigen Receptor Reveals Potential Off-Target Interactions due to the IgG2 CH2-CH3 CAR-Spacer. Journal of Immunology Research. 2015. Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1068490
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1068490