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Single variable domains from the T cell receptor ? chain function as mono- and bifunctional CARs and TCRs.


ABSTRACT: Cell therapy using T cell receptors (TCRs) and chimeric antigen receptors (CARs) represents a new wave of immunotherapies garnering considerable attention and investment. Further progress in this area of medicine depends in part on improving the functional capabilities of the engineered components, while maintaining the overall size of recombinant constructs to ensure their compatibility with existing gene delivery vehicles. We describe a single-variable-domain TCR (svd TCR) that utilizes only the variable domain of the ? chain (V?). This V? module not only works in TCR and CAR formats, but also can be used to create single-chain bispecific CARs and TCRs. Comparison of individual ligand-binding V? domains in different formats suggests that the lone V? sequence controls the sensitivity and a major part of the specificity of the CAR or TCR construct, regardless of signaling format, in Jurkat and primary T cells.

SUBMITTER: Oh J 

PROVIDER: S-EPMC6872726 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Single variable domains from the T cell receptor β chain function as mono- and bifunctional CARs and TCRs.

Oh Julyun J   Warshaviak Dora Toledo DT   Mkrtichyan Mikayel M   Munguia Melanie Lisette ML   Lin Abby A   Chai Falene F   Pigott Craig C   Kang Jaspal J   Gallo Michael M   Kamb Alexander A  

Scientific reports 20191121 1


Cell therapy using T cell receptors (TCRs) and chimeric antigen receptors (CARs) represents a new wave of immunotherapies garnering considerable attention and investment. Further progress in this area of medicine depends in part on improving the functional capabilities of the engineered components, while maintaining the overall size of recombinant constructs to ensure their compatibility with existing gene delivery vehicles. We describe a single-variable-domain TCR (svd TCR) that utilizes only t  ...[more]

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