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Immuno-checkpoint therapy significantly improves the prognosmation of treatment for certain cancers.
cytokine inhibitor signal family protein plays an important role in physiological activity and anti-tumor toxicity of NK cells.
protein (CIS) that contains the SH2 domain, encoded by the CSIS gene, is a member of the family.
in order to extend the clinical effects of checkpoint targeting, Daher and others have designed a joint strategy to combine lecytocyte interlethional (IL)-15-CAR engineering with NK cells that knock out the source of CISH's cord blood (CB).
this joint strategy can enhance NK cell effector function by enhancing the Akt/mTORC1 axis and c-MYC signals, thereby increasing aerobic glycolysis.
(CRISPR/Cas9-mediated knock-out of THECH) was tested in mouse models of lymphoma, and this joint method improved the anti-tumor activity of NK cells more than one of them alone, eliminating lymphoma allogeneic transplantation without any detectable signs of toxicity.
(survival rates in mice with lymphoma treated with different strategies), the researchers concluded that targeted cytokine checkpoints could further enhance the anti-tumor activity of CAR-NK cells that secrete IL-15 by promoting their metabolic suitability and anti-tumor activity.
this combination represents a promising milestone in the development of a new generation of NK cells for cancer immunotherapy.
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