激活「基因组守护者」p53可让抗癌T细胞更持久：UCLA团队找到强化免疫疗法的新办法
位于加利福尼亚州洛杉矶县洛杉矶市的加州大学洛杉矶分校（UCLA）10月29日发布研究成果：该校 Jonsson 综合癌症中心团队发现，在制备工程化T细胞时短暂激活以防癌著称的蛋白质 p53，可让这些免疫细胞更强、更持久，为提升现有癌症免疫疗法的效果提供了一条相对简单的路径。研究发表于《免疫学前沿》（Frontiers in Immunology）。
T细胞疗法的一大瓶颈是「耗竭」：回输体内的T细胞久战之后会逐渐失去杀伤力。研究团队用试验药物 navtemadlin 阻断会抑制 p53 的蛋白质 MDM2，短暂激活 p53 后发现，处理过的人类 CD8+ T细胞耗竭迹象更少、能量储备更高，在实验室中清除黑色素瘤细胞的能力明显更强，约四十小时后开始显现优势并持续全程。剂量同样关键：低剂量有助于生成健康的记忆T细胞，高剂量则会造成更多细胞死亡。
论文资深作者、UCLA 大卫·格芬医学院外科助理教授 Joseph Crompton 表示，这是首批把 p53 与人类T细胞耗竭联系起来的研究之一；p53 长期以来以防癌闻名，而新发现提示它同样能帮助免疫细胞保持抗癌能力。研究人员指出，这一方法是在细胞制备环节加一道药物处理，无需额外的基因改造。
Activating p53 Makes Cancer-Fighting T Cells Stronger and Longer-Lasting, UCLA Study Finds
The University of California, Los Angeles, in the City of Los Angeles, Los Angeles County, California, announced on October 29 that researchers at its Jonsson Comprehensive Cancer Center have found that temporarily activating p53, a protein best known for preventing cancer, during the preparation of engineered T cells makes those immune cells stronger and longer-lasting, offering a relatively simple way to improve existing cancer immunotherapies. The study was published in Frontiers in Immunology.
A key limit on T-cell therapy is exhaustion: infused T cells gradually lose their killing power. The team used the investigational drug navtemadlin to block MDM2, a protein that keeps p53 in check, and found that treated human CD8+ T cells showed fewer signs of exhaustion, held greater energy reserves, and killed melanoma cells in the laboratory significantly more effectively, pulling ahead after about 40 hours and keeping the advantage throughout. Dose mattered: lower concentrations promoted healthy memory T cells, while higher ones caused more cell death.
Senior author Joseph Crompton, an assistant professor of surgery at UCLA's David Geffen School of Medicine, said this is one of the first studies to link p53 to T-cell exhaustion in humans; long known for preventing cancer, p53 may also help immune cells maintain their ability to fight it. The researchers noted the approach adds a drug step during cell preparation, with no additional genetic modification required.
来源：GSM·美国（原文链接）
图片来源：T细胞疗法示意图（资料图）。公共领域图片，Wikimedia Commons。 / An illustration of T-cell therapy (file image). Public domain, via Wikimedia Commons.
