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• W1502247133 endingPage "154" @default.
• W1502247133 startingPage "145" @default.
• W1502247133 abstract "Abstract T cells of tumor bearers often show defective TCR-mediated signaling events and, therefore, exhibit impaired immune responses. As such, patients with heavy tumor burden are often not amenable to adoptive T cell therapy. To overcome this limitation, we have developed a chimeric receptor that joins an extracellular single chain Fv (scFv) of a specific Ab for Ag recognition to an intracellular protein tyrosine kinase (PTK) for signal propagation. Stimulation through the scFv-PTK receptor should bypass defective TCR-proximal events and directly access the T cell’s effector mechanisms. In this study we describe the optimization of a scFv-PTK configuration, leading to complete T cell activation. The cytosolic PTK Syk is superior to its family member, Zap-70, for intracellular signaling. As a transmembrane (TM) domain, CD4 performs better than CD8 when plastic-immobilized Ag serves as a stimulator. However, when APC are used to trigger chimeric receptors, the need for a flexible spacer between the scFv and TM domains becomes apparent. The CD8α-derived hinge successfully performs this task in chimeric scFv-Syk receptors regardless of its cysteine content. A cytotoxic T cell hybridoma expressing chimeric receptor genes composed of scFv-CD8hinge-CD8TM-Syk or scFv-CD8hinge-CD4TM-Syk is efficiently stimulated to produce IL-2 upon interaction with APC and specifically lyses appropriate target cells in a non-MHC-restricted manner." @default.
• W1502247133 created "2016-06-24" @default.
• W1502247133 creator A5007314803 @default.
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• W1502247133 date "1998-01-01" @default.
• W1502247133 modified "2023-10-16" @default.
• W1502247133 title "Harnessing Syk Family Tyrosine Kinases as Signaling Domains for Chimeric Single Chain of the Variable Domain Receptors: Optimal Design for T Cell Activation" @default.
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• W1502247133 doi "https://doi.org/10.4049/jimmunol.160.1.145" @default.
• W1502247133 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9551966" @default.
• W1502247133 hasPublicationYear "1998" @default.
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