Immix Biopharma Investor Presentation Deck
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CD32
Proprietary Optimized CD33+ CD8 Delivers "Digital” Intracellular Signaling, Eliminates
Neurotoxicity, Reduces CRS Duration
CARS rely on activation of CAR-T cells through CD32 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, therefore:
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 than a traditional
CAR
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
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
Source:: Feucht J, et al. Nat Med. 2019; Shah K, et al. Signal Transduct Target Ther. 2021
CD3
14-1BB
4-1BB
ITAM domain
nature
Signal Transduction
and Targeted Therapy
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IMMİX
S BIOPHARMA
"In activated T cells, the CD32
chain gets ubiquitinated by CBLB
at its multiple lysine residues and
induces degradation of surface
TCRs"
doi: 10.1038/s41392-021-00823-w
Memorial Sloan Kettering
Cancer Center
medicine
"We hypothesized that the redundancy of CD28 and CD32 signaling in a chimeric
antigen receptor (CAR) design incorporating all three CD32 immunoreceptor
tyrosine-based activation motifs (ITAMs)11,13 may foster counterproductive T
cell differentiation and exhaustion. Therefore, we calibrated ITAM activity by
mutating tyrosine residues to impede their phosphorylation and downstream
signaling"
doi: 10.1038/s41591-018-0290-5
11View entire presentation