A TCR-based Chimeric Antigen Receptor

Abstract Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antig...

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Autores principales:	Even Walseng, Hakan Köksal, Ibrahim M. Sektioglu, Anne Fåne, Gjertrud Skorstad, Gunnar Kvalheim, Gustav Gaudernack, Else Marit Inderberg, Sébastien Wälchli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e8a6236e1d04796a5c036d02bcd1d20
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spelling	oai:doaj.org-article:0e8a6236e1d04796a5c036d02bcd1d202021-12-02T15:04:53ZA TCR-based Chimeric Antigen Receptor10.1038/s41598-017-11126-y2045-2322https://doaj.org/article/0e8a6236e1d04796a5c036d02bcd1d202017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-11126-yhttps://doaj.org/toc/2045-2322Abstract Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells. Hence, an introduced therapeutic TCR will compete with the endogenous TCR for the signalling proteins and carries the potential risk of mixed dimer formation giving rise to a new TCR with unpredictable specificity. We have fused a soluble TCR construct to a CAR-signalling tail and named the final product TCR-CAR. We here show that, if expressed, the TCR-CAR conserved the specificity and the functionality of the original TCR. In addition, we demonstrate that TCR-CAR redirection was not restricted to T cells. Indeed, after transduction, the NK cell line NK-92 became TCR positive and reacted against pMHC target. This opens therapeutic avenues combing the killing efficiency of NK cells with the diversified target recognition of TCRs.Even WalsengHakan KöksalIbrahim M. SektiogluAnne FåneGjertrud SkorstadGunnar KvalheimGustav GaudernackElse Marit InderbergSébastien WälchliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Even Walseng Hakan Köksal Ibrahim M. Sektioglu Anne Fåne Gjertrud Skorstad Gunnar Kvalheim Gustav Gaudernack Else Marit Inderberg Sébastien Wälchli A TCR-based Chimeric Antigen Receptor
description	Abstract Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells. Hence, an introduced therapeutic TCR will compete with the endogenous TCR for the signalling proteins and carries the potential risk of mixed dimer formation giving rise to a new TCR with unpredictable specificity. We have fused a soluble TCR construct to a CAR-signalling tail and named the final product TCR-CAR. We here show that, if expressed, the TCR-CAR conserved the specificity and the functionality of the original TCR. In addition, we demonstrate that TCR-CAR redirection was not restricted to T cells. Indeed, after transduction, the NK cell line NK-92 became TCR positive and reacted against pMHC target. This opens therapeutic avenues combing the killing efficiency of NK cells with the diversified target recognition of TCRs.
format	article
author	Even Walseng Hakan Köksal Ibrahim M. Sektioglu Anne Fåne Gjertrud Skorstad Gunnar Kvalheim Gustav Gaudernack Else Marit Inderberg Sébastien Wälchli
author_facet	Even Walseng Hakan Köksal Ibrahim M. Sektioglu Anne Fåne Gjertrud Skorstad Gunnar Kvalheim Gustav Gaudernack Else Marit Inderberg Sébastien Wälchli
author_sort	Even Walseng
title	A TCR-based Chimeric Antigen Receptor
title_short	A TCR-based Chimeric Antigen Receptor
title_full	A TCR-based Chimeric Antigen Receptor
title_fullStr	A TCR-based Chimeric Antigen Receptor
title_full_unstemmed	A TCR-based Chimeric Antigen Receptor
title_sort	tcr-based chimeric antigen receptor
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0e8a6236e1d04796a5c036d02bcd1d20
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A TCR-based Chimeric Antigen Receptor

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