T cells modified with synthetic receptors containing single ITAM signaling motif
A signaling, genetic modification technology for biotechnology and cell therapy applications
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[0047] The inventors of the present application have discovered that in genetically modifying T cells, in particular αβ T cells, to express a co-stimulatory signaling domain containing at least one co-stimulatory signaling domain and containing only one immunoreceptor tyrosine-based activation motif (ITAM) Genetically modified T cells exhibit enhanced cell expansion, reduced cytokine release, and reduced xenograft-versus-host disease (GvHD) following intracellular signaling domain chimeric antigen receptor (CAR).
[0048] Accordingly, in one example, the present invention relates to a recombinant chimeric antigen receptor (CAR), wherein the recombinant CAR comprises: (a) an extracellular domain comprising an antigen binding region, (b) a transmembrane domain, ( c) at least one costimulatory signaling domain, and (d) an intracellular signaling domain, wherein the extracellular domain comprises the extracellular domain of NK cell activating receptor or the scFv of a monoclonal an...
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