Upon further exploration, it appears the possible constructs that may be subject to this sponsored research agreement (based on information from on the patent US2016/056901) include the following:
1. CTLX
2. an insert related to CTLX i.e. GaTx2, a toxin from Leiurus quinquestriatus hebraeus,
3. more than one CTLX or related sequence
4. GaTxl, a toxin from Leiurus quinquestriatus hebraeus
5. AaCtx, a toxin from Androctonus australis
6. BmKCT, a toxin from Buthus martensii
7. A variant of CTLX as specified in the patent
8. Or a specific modification to certain costimulatory domains as specified in the patent
Another part of the patent that caught my attention was the following:
"One CAR comprising chlorotoxin described herein is referred to as CLTX-IgG4(EQ)-CD28gg-Zeta. This CAR includes a variety of important features including: chlorotoxin; an IgG4 Fc region that is mutated at two sites within the CH2 region (L235E; N297Q) in a manner that reduces binding by Fc receptors (FcRs); domain, a CD28 co-stimulatory domain, and Οϋ3ζ activation domain"
I wonder to what extent this reduced binding by Fc receptors is the reason why the treatment doesn't seem to induce a cytokine storm that is often seen with other Car T cell therapies.
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