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...
嵌合抗原受体T(chimeric antigen receptor modified T,CAR-T)细胞是利用基因工程技术,将能识别某种肿瘤抗原的特异性单链单克隆抗体的抗原结合部与T细胞受体的酪氨酸活化基序及信号蛋白偶联为一个嵌合分子,通过病毒载体或其他基因编辑方法整合到T细胞...
CAR-T cells were incubated in the presence of dasatinib or vehicle and stimulated with 5 mg/mL anti-FMC63 idiotype 1 5 mg/mL goat anti-mouse secondary antibody for 5 minutes. Whole-cell protein lysates were obtained in nondenaturing buffer (150 mmol/L NaCl, 50 mmol/L Tris-pH8, 1% NP...
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.
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 ...
After 24-h 1 mM dasatinib treatment, levels of pSrc (at Y418) are decreased in all cell lines, and of pAKT in OUMS27, L835, L3252, JJ012 and NDCS-1. (B) Immunoblotting showing p53, MDM2 and p21 in untreated chondrosarcoma cell lines (Mock) and after 24-h 1 mM dasatinib. ...
Respiratory quotient (RQ) is the ratio of car- bon dioxide produced and oxygen consumed by the body, reflecting substrate utilization for energy gen- eration. In the current study, RQ in Fisetin treated male C57BL/6 mice was reduced indicating a shift in metabolic substrate utilization from ...
Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling 2021, Science OX40 agonists and combination immunotherapy: Putting the pedal to the metal 2015, Frontiers in Oncology View all citing articles on Scopus ...
Peak expansion of CD123-CAR.dasa T cells, as judged by qPCR analysis, was higher in comparison to CD123-CAR T cells. However, this did not translate into improved anti-leukemia activity as no patients had a response. Conclusions CD123-CAR T cells generated in the presence of dasatinib ...