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  "notes": "The slide uses external citations from Nature Medicine and Signal Transduction and Targeted Therapy to validate the scientific approach of ITAM modification.",
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      "text": "NXC-201 adds a positively charged amino acid (lysine) next to a tyrosine phosphorylation site, therefore: Impeding phosphorylation of ITAM1, thus reducing intracellular reactivity; Adding an additional site for ubiquitination, allowing more rapid degradation",
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      "text": "CARs rely on activation of CAR-T cells through CD3ζ derived immunoreceptor tyrosine-based activation motifs (ITAMs), typically 3 ITAM motifs per CAR",
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      "text": "Modification of ITAMs is a common theme in third-generation CAR design, with publications in Nature Medicine and by Memorial Sloan Kettering on the topic",
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      "text": "The combined effect of these modifications is to drive a “digital” signaling of extracellular activity, that is on when antigen is present and off when not",
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      "text": "In activated T cells, the CD3ζ chain gets ubiquitinated by CBLB at its multiple lysine residues and induces degradation of surface TCRs",
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      "text": "We hypothesized that the redundancy of CD28 and CD3ζ signaling in a chimeric antigen receptor (CAR) design incorporating all three CD3ζ ITAMs may foster counterproductive T cell differentiation and exhaustion. Therefore, we calibrated ITAM activity by mutating tyrosine residues to impede their phosphorylation and downstream signaling",
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      "text": "Source:: Feucht J, et al. Nat Med. 2019; Shah K, et al. Signal Transduct Target Ther. 2021",
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      "kind": "title",
      "text": "Proprietary Optimized CD3ζ + CD8 Delivers “Digital” Intracellular Signaling, Eliminates Neurotoxicity, Reduces CRS Duration",
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