肿瘤细胞治疗研究
英文原题：KLRG1 silencing increases the efficacy of CAR NK cell therapy against colon cancer via SHP-2/ZAP-70/NF-κB signal pathway.
KLRG1 silencing increases the efficacy of CAR NK cell therapy against colon cancer via SHP-2/ZAP-70/NF-κB signal pathway.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
我们的研究证明，下调 KLRG1 可增强 CAR NK 细胞的抗肿瘤活性，为 CAR NK 细胞治疗提供了新思路。
为研究 KLRG1 对 CAR-NK 功能的调节作用，研究者利用基因沉默技术构建 KLRG1 敲低的 NKG2D-CAR，并将其转导至 NK92 细胞。通过体外和体内实验，评估 KLRG1 干预的 NKG2D-CAR-NK 细胞对结直肠癌的作用。
研究发现，敲低 KLRG1 可通过提高 CD69、CD107a、IFN-γ、颗粒酶 B（GzmB）、穿孔素和 TNF-α 表达，增强 CAR-NK 细胞体内外的抗结肠癌细胞毒性。此外，KLRG1 缺失改善 CAR-NK 细胞增殖和存活，同时降低其耗竭。机制上，KLRG1 通过 ZAP-70/NF-κB 信号轴调节 CAR-NK 功能。
本研究表明，下调 KLRG1 可增强 CAR-NK 细胞抗肿瘤活性，为 CAR-NK 细胞治疗提供新思路。
NK cells are the core cells of the innate immune system, which can kill cancer cells non-specifically and almost do not cause immune rejection or neurotoxicity, thereby enabling broad application in immune cell therapy. The KLRG1/Cadherin signaling axis has been reported to inhibit the anti-tumor response of NK cells. However, the mechanism by which KLRG1 regulates CAR NK cell function remains unclear.
To investigate the regulatory role of KLRG1 in CAR NK cell function, we constructed a KLRG1-knockdown NKG2D-CAR construct using gene-silencing techniques and transduced it into NK92 cells. Through in vitro and in vivo experiments, we examined the effects of KLRG1-interfered NKG2D-CAR NK cells on colorectal cancer.
Our findings suggest that KLRG1 knockdown enhanced the anti-colon cancer cytotoxicity of CAR NK cells by increasing the expression of CD69, CD107a, IFN- , GzmB, Perforin, and TNF- both in vitro and in vivo. Additionally, KLRG1 deficiency improved the proliferation and survival of CAR NK cells while reducing their depletion. Mechanically, KLRG1 regulates CAR NK cell function through the ZAP-70/NF- B signaling axis.
Our study demonstrated that down-regulation of KLRG1 enhanced the anti-tumor activity of CAR NK cells, providing a new idea for CAR NK cell therapy.
MEMBER ACCOUNT
登录成功会直接打开下一页。
