Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML).

Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML). Research Abstract Details 

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Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML). Abstract Text:

W Yang,E L Beaudoin,L Lu,R A Du Pasquier,M J Kuroda,R A Willemsen,I J Koralnik,R P Junghans,W Yang,E L Beaudoin,L Lu,R A Du Pasquier,M J Kuroda,R A Willemsen,I J Koralnik,R P Junghans,

Progressive multifocal leukoencephalopathy (PML) is a deadly brain disease caused by the polyomavirus JC (JCV). The aim of this study is to develop 'designer T cells' armed with anti-JCV TCR-based chimeric immune receptors (CIRs) by gene modification for PML immunotherapy. Two T cell lines specific to two dominant CTL epitopes derived from JCV VP1 protein (termed p36 and p100) from an HLA-A0201+ PML survivor were generated for TCR cloning. Two distinct dominant TCR alpha chains (Valpha6 and Valpha12) and a unique TCR beta chain (Vbeta5.1) were cloned from the p36-specific cell line, while only one alpha (Valpha8.6) and one beta (Vbeta2) chains were dominant in the p100-specific line. Retroviral constructs encoding CIRs were created with the extracellular domains of TCR alpha and beta chains fused to the transmembrane and cytoplasmic portions of CD3zeta (ValphaCalphaCD3zeta or VbetaCbetaCD3zeta). Cellular expression and screening for binding specific peptide-HLA-A0201 tetramer confirmed the reactivity of the p100 TCRalphabeta and of one of the two pairs of p36 TCRalphabeta (Valpha12 and Vbeta5.1). Functional tests confirmed CIR-expressing T cells secreted cytokines and expressed potent cytotoxicity on contact with A0201+ B-lymphoblastoid line loaded with peptides and/or with HLA-A0201+ cells expressing native JCV VP1 protein. In conclusion, anti-JCV designer T cells were generated.

Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML). Publishing Authors By Initials

W Yang,EL Beaudoin,L Lu,RA Du Pasquier,MJ Kuroda,RA Willemsen,IJ Koralnik,RP Junghans,W Yang,EL Beaudoin,L Lu,RA Du Pasquier,MJ Kuroda,RA Willemsen,IJ Koralnik,RP Junghans,

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Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML). Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: International immunology

VOLUME: 19

Page Numbers: 1083-93

Journal Abbreviation: Int. Immunol.

ISSN: 0953-8178

DAY: 28

MONTH: 07

YEAR: 2007

Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML). Information

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LANGUAGE: eng

NlmUniqueID: 8916182

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Grant and Affiliation Information for Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML).

AFFILIATION: Division of Surgical Research, Department of Surgery, Boston University School of Medicine, Roger Williams Medical Center, Providence, RI 02908, USA.

Country: England

AGENCY: United States NIAID

GRANT: R01NS/AI041198

ACRONYM: AI

MEDLINETA: Int Immunol

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