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  "documentTitle": "Immix Biopharma | Investor Presentation Deck | 60 slides",
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  "presentationDate": "2023-11-01 00:00:00",
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  "notes": "The slide uses authority-citation to validate the mechanism of ITAM modification and degradation.",
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      "kind": "image",
      "text": "Diagram of CD3ζ/4-1BB domain structure",
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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. NXC-201 adds a positively charged amino acid (lysine) next to a tyrosine phosphorylation site.",
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      "text": "Impeding phosphorylation of ITAM1 (by affecting protein folding dynamics which block the tyrosine site), thus reducing intracellular reactivity. Adding an additional site for ubiquitination, allowing the CAR to be marked for degradation more rapidly.",
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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... may foster counterproductive T cell differentiation and exhaustion. Therefore, we calibrated ITAM activity by mutating tyrosine residues to impede their phosphorylation",
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      "kind": "source-note",
      "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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