Molecular Characterization of a Fully Human Chimeric T-Cell Antigen Receptor for Tumor-Associated Antigen EpCAM
Joint Authors
Kuroki, Motomu
Kuroki, Masahide
Yamada, Hiromi
Shibaguchi, Hirotomo
Shirasu, Naoto
Source
Journal of Biomedicine and Biotechnology
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-04-03
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
The transduction of T cells to express chimeric T-cell antigen receptor (CAR) is an attractive strategy for adaptive immunotherapy for cancer, because the CAR can redirect the recognition specificity of T cells to tumor-associated antigens (TAAs) on the surface of target cells, thereby avoiding the limitations of HLA restriction.
However, there are considerable problems with the clinical application of CAR, mostly due to its xenogeneic components, which could be immunogenic in humans.
Moreover, while extensive studies on the CARs have been performed, the detailed molecular mechanisms underlying the activation of CAR-grafted T cells remain unclear.
In order to eliminate potential immunogenicity and investigate the molecular basis of the CAR-mediated T-cell activation, we constructed a novel CAR (CAR57-28ζ) specific for one of the most important TAAs, epithelial cell adhesion molecule (EpCAM), using only human-derived genes.
We revealed that in Jurkat T cells, lentivirally expressed CAR57-28ζ can transmit the T-cell-activating signals sufficient to induce IL-2 production upon EpCAM stimulation.
An immunofluorescent analysis clearly showed that the CAR57-28ζ induces the formation of signaling clusters containing endogenous CD3ζ at the CAR/EpCAM interaction interface.
These results suggest that this CAR gene may be safely and effectively applied for adaptive T-cell immunotherapy.
American Psychological Association (APA)
Shirasu, Naoto& Yamada, Hiromi& Shibaguchi, Hirotomo& Kuroki, Motomu& Kuroki, Masahide. 2012. Molecular Characterization of a Fully Human Chimeric T-Cell Antigen Receptor for Tumor-Associated Antigen EpCAM. Journal of Biomedicine and Biotechnology،Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-503559
Modern Language Association (MLA)
Shirasu, Naoto…[et al.]. Molecular Characterization of a Fully Human Chimeric T-Cell Antigen Receptor for Tumor-Associated Antigen EpCAM. Journal of Biomedicine and Biotechnology No. 2012 (2012), pp.1-7.
https://search.emarefa.net/detail/BIM-503559
American Medical Association (AMA)
Shirasu, Naoto& Yamada, Hiromi& Shibaguchi, Hirotomo& Kuroki, Motomu& Kuroki, Masahide. Molecular Characterization of a Fully Human Chimeric T-Cell Antigen Receptor for Tumor-Associated Antigen EpCAM. Journal of Biomedicine and Biotechnology. 2012. Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-503559
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-503559