本文由定制化企业智能智能服务平台——【智强企业】提供。
标签： T细胞
宾夕法尼亚大学的研究人员报告说，p53 蛋白的变体可能会增加嵌合抗原受体 （CAR） T 细胞的有效性**。
researchers at the university of pennsylvania report a variant of the p53 protein may improve the effectiveness of chimeric antigen receptor (car) t cell therapy.
研究结果发表在《美国国家科学院院刊》上，作者是病理学和检验医学系免疫学系的Richard W.由Vague教授领导的Carl June博士，他是佩雷尔曼医学院细胞免疫中心**主任和宾夕法尼亚大学帕克癌症免疫研究所**主任。
the findings are published in the proceedings of the national academy of sciences and led by carl june, md, the richard w. vague professor in immunotherapy in the department of pathology and laboratory medicine, director of the center for cellular immunotherapies at the perelman school of medicine, and director of the parker institute for cancer immunotherapy at the university of pennsylvania.
“CAR T细胞是血癌的一种转化形式，受到T细胞功能障碍的限制，特别是在慢性淋巴细胞白血病（CLL）中，”研究人员写道。 ”。我们的研究揭示了人类和猿特异性 p53 亚型 δ133p53 在增强 CAR T 细胞的作用中的关键作用**。 δ133P53A在CAR T淋巴细胞中的表达可以提高其代谢稳定性，使其具有优越的抗肿瘤功能，特别是在高肿瘤负荷条件下。 ”
car t cell therapy, a transformative treatment for blood cancers, is limited by t cell dysfunction, especially in chronic lymphocytic leukemia (cll),”the researchers wrote. “our study reveals a pivotal role for the human and great ape-specific p53 isoform, δ133p53α, in enhancing the therapeutic efficacy of car t cells. expressing δ133p53α in car t cells improves their metabolic robustness, enabling superior antitumor function particularly under high tumor burden conditions.”
June及其同事靶向p53蛋白变体δ133p53，其在人类T细胞中的表达随着年龄的增长而降低。
june and colleagues targeted the p53 protein variant δ133p53α, which decreases in expression with age in human t cells.
在临床试验中，133p53 的持续表达改善了由健康正常供体和 CAR T 细胞难治的 CLL 患者**制成的 CAR T 淋巴细胞的抗肿瘤功能。 δ133p53在CAR T细胞中的表达可增强细胞代谢功能并增强抗肿瘤活性，尤其是在肿瘤负荷高的条件下。 在营养限制条件下，表达δ133P53的CAR T细胞不仅清除了更多的肿瘤，而且增殖了更多，部分原因是关键生物合成过程的增强和线粒体功能的改善。
continual expression of δ133p53α improved the antitumor function of car t cells manufactured from both healthy normal donors and from people with cll who failed to respond to car t cell therapy during clinical trials. expressing δ133p53α in car t cells enhanced the cells’ metabolic function, boosting antitumor activity, especially under conditions of high tumor burden. under nutrient-limiting conditions, car t cells expressing δ133p53α not only cleared significantly more tumor but also displayed increased proliferation, partly due to the enhancement of key biosynthetic processes and improved mitochondrial function.
这些发现指出了p53信号转导网络作为延长CAR T细胞反应调节剂的重要作用，并为抗癌T细胞的利用提供了新的途径。
the findings point to the significant role of the p53 signaling network as a regulator of prolonged car t cell responses and provides new **enues of therapies that harness cancer-fighting t cell
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