该研究模拟CAR-T细胞肿瘤抗原暴露场景,在完成肿瘤细胞杀伤后的CAR-T细胞中添加达沙替尼,发现分化后的CAR-T细胞几乎可完全逆转成为中心记忆性CAR-T细胞,耗竭相关抑制性受体PD1、TIM3和LAG3的表达明显下调,且增殖能力得到了显著的提高。 研究者进一步通过RNA测序分析,发现达沙替尼处理的CAR-T细胞活化信号通路如T cell rec...
该研究模拟CAR-T细胞肿瘤抗原暴露场景,在完成肿瘤细胞杀伤后的CAR-T细胞中添加Dasatinib,发现分化后的CAR-T细胞几乎可完全逆转成为中心记忆性CAR-T细胞,耗竭相关抑制性受体PD1、TIM3和LAG3的表达明显下调,且增殖能力得到了显著的提高。 研究者进一步...
使用达沙替尼后,细胞溶解活性,细胞因子产生和CAR-T细胞的增殖都受到了影响,从而实现CAR-T细胞功能的部分或完全抑制。 在停用达沙替尼后,抑制作用迅速完全逆转,不会影响CAR-T细胞的活性,马上恢复其抗肿瘤功能。 研究表明,达沙替尼的抑制CAR-T的效果优于地塞米松,而地塞米松的作用具有迟发性和不完全性,所以达沙替尼可...
我们团队对于Ph阳性急性淋巴细胞白血病,尤其是未获得缓解的患者,也会采用针对CD19或CD20的CAR-T细胞治疗后再进行造血干细胞移植。 对于急性髓系白血病,非移植治疗的疗效没有急性淋巴细胞白血病好,无病生存率约在60%～70%之间,所以还有一部分患者需要造血干细胞移植,移植前可以使用针对髓系白血病的CAR-T细胞、靶向药物...
In this single center experience, dasatinib improved neurotoxicity in CAR-T patients with steroid refractory ICANS. More studies are needed to evaluate its use and underlying mechanisms.doi:10.1016/j.jtct.2025.01.370Muhammad Junaid TariqRoswell Park Comprehensive Cancer Center, Buffalo, NYShowkat Hamid...
Such effect could unexpectedly switch off the antitumor activity, albeit reversible, of CAR-T cells (Mestermann et al., 2019; Rivera-Torres & Esther San José, 2019; Shade et al., 2008). Other concerns of relevance derive from SKF inhibition, which interfere with vascular and immune ...
T315I mutation exerts a dismal prognosis on adult BCR-ABL1-positive acute lymphoblastic leukemia, and salvage therapy with ponatinib or CAR-T cell and bridging to allogeneic hematopoietic stem cell transplantation can improve clinical outcomes. Annals of Hematology 99: 829-834, No. 4, Apr 2020. ...
Dasatinib is an oral available short-acting inhibitor of multiple tyrosine kinases. It was designed to inhibit ABL and SRC, but also has activity in multiple other kinases, including c-KIT, PDGFR-α, PDGFR-β, and ephrin receptor kinases. Dasatinib is a.
For this, we measured phosphorylation states of Akt and ERK in CFb and car- diomyocytes following stimulation with insulin and PDGF (Fig 6D). Akt and ERK activation is critical for cell survival and proliferation, respectively. Both Akt and ERK activation by PDGF was substantially...
Activation of AKT1 can be through mutations in the pleckstrin homology domain, found mostly in solid tumours (Mahajan and Mahajan, 2012), leading to activated downstream signalling and decreased sensitivity to kinase inhibitors (Carpten et al, 2007). Hotspot mutations in the pleckstrin homology ...