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Building and Optimizing a Virus-specific T Cell Receptor Library for Targeted Immunotherapy in Viral Infections

Identifieur interne : 001182 ( Main/Exploration ); précédent : 001181; suivant : 001183

Building and Optimizing a Virus-specific T Cell Receptor Library for Targeted Immunotherapy in Viral Infections

Auteurs : Nasirah Banu ; Adeline Chia ; Zi Zong Ho ; Alfonso Tan Garcia ; Komathi Paravasivam ; Gijsbert M. Grotenbreg ; Antonio Bertoletti ; Adam J. Gehring

Source :

RBID : PMC:3933865

Abstract

Restoration of antigen-specific T cell immunity has the potential to clear persistent viral infection. T cell receptor (TCR) gene therapy can reconstitute CD8 T cell immunity in chronic patients. We cloned 10 virus-specific TCRs targeting 5 different viruses, causing chronic and acute infection. All 10 TCR genetic constructs were optimized for expression using a P2A sequence, codon optimization and the addition of a non-native disulfide bond. However, maximum TCR expression was only achieved after establishing the optimal orientation of the alpha and beta chains in the expression cassette; 9/10 TCRs favored the beta-P2A-alpha orientation over alpha-P2A-beta. Optimal TCR expression was associated with a significant increase in the frequency of IFN-gamma+ T cells. In addition, activating cells for transduction in the presence of Toll-like receptor ligands further enhanced IFN-gamma production. Thus, we have built a virus-specific TCR library that has potential for therapeutic intervention in chronic viral infection or virus-related cancers.


Url:
DOI: 10.1038/srep04166
PubMed: 24566718
PubMed Central: 3933865


Affiliations:


Links toward previous steps (curation, corpus...)


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<name sortKey="Strominger, Jl" uniqKey="Strominger J">JL Strominger</name>
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<analytic>
<author>
<name sortKey="Labrecque, N" uniqKey="Labrecque N">N Labrecque</name>
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<analytic>
<author>
<name sortKey="Leen, Am" uniqKey="Leen A">AM Leen</name>
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<author>
<name sortKey="Chang, Cxl" uniqKey="Chang C">CXL Chang</name>
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<list></list>
<tree>
<noCountry>
<name sortKey="Banu, Nasirah" sort="Banu, Nasirah" uniqKey="Banu N" first="Nasirah" last="Banu">Nasirah Banu</name>
<name sortKey="Bertoletti, Antonio" sort="Bertoletti, Antonio" uniqKey="Bertoletti A" first="Antonio" last="Bertoletti">Antonio Bertoletti</name>
<name sortKey="Chia, Adeline" sort="Chia, Adeline" uniqKey="Chia A" first="Adeline" last="Chia">Adeline Chia</name>
<name sortKey="Garcia, Alfonso Tan" sort="Garcia, Alfonso Tan" uniqKey="Garcia A" first="Alfonso Tan" last="Garcia">Alfonso Tan Garcia</name>
<name sortKey="Gehring, Adam J" sort="Gehring, Adam J" uniqKey="Gehring A" first="Adam J." last="Gehring">Adam J. Gehring</name>
<name sortKey="Grotenbreg, Gijsbert M" sort="Grotenbreg, Gijsbert M" uniqKey="Grotenbreg G" first="Gijsbert M." last="Grotenbreg">Gijsbert M. Grotenbreg</name>
<name sortKey="Ho, Zi Zong" sort="Ho, Zi Zong" uniqKey="Ho Z" first="Zi Zong" last="Ho">Zi Zong Ho</name>
<name sortKey="Paravasivam, Komathi" sort="Paravasivam, Komathi" uniqKey="Paravasivam K" first="Komathi" last="Paravasivam">Komathi Paravasivam</name>
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