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Wednesday, 06/08/2022 11:32:20 PM

Wednesday, June 08, 2022 11:32:20 PM

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From 10K:
Importantly, our one-step genome editing
approach avoids making multiple breaks to the T cell’s DNA and also contributes to minimizing cell processing time, which helps prevent the
CAR T cells from differentiating during the process.
• Novel co-stimulatory domain. Our genetically engineered CAR T cells incorporate a novel, proprietary, costimulatory domain called N6, which
may enable us to enhance cell proliferation and effector function while preserving cell phenotype. We engineered N6 to improve on the function
of the 4-1bb costimulatory domain commonly used in autologous CAR T products. Our preclinical data suggests that, compared to 4-1bb, N6
provides an activation signal to the CAR T cells that better preserves cell expansion potential while maintaining naïve cell phenotype following
exposure to cancer cells. We also believe N6 can help avoid CAR T cell hyperstimulation, which can contribute to adverse events seen with
autologous products.
This allows us to “fine-tune” the CAR T cells to ensure that they respond appropriately to the cancer but do not become
hyper-activated or exhausted. The below comparison demonstrates the difference in consistency achieved by using lentivirus delivery compared
with targeted delivery through an ARCUS nuclease. CAR T cells produced using ARCUS exhibit reduced cell-to-cell variability as well as more
controlled levels of CAR gene expression depending on whether the cells are tuned for high expression or low expression.
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