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在卵巢癌中向CA125的基于干的采用T细胞向CA125

Haihong Zhao¹, Lina Wu¹, Jiemin Dai¹

¹Department of Obstetrics and Gynecology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China.

Journal of translational medicine

|September 5, 2023

概括

这项研究开发了一种新型的卵巢癌治疗方法,使用嵌合式受体 (CR) 和嵌合式抗原受体 (CAR) 向CA125. 同时表达CR和CART细胞在小鼠中表现出优异的卵巢癌细胞杀死和改善生存率.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
生物技术是生物技术.

背景情况:

卵巢癌 (OC) 是一种具有糟糕生存率的侵袭性恶性瘤,通常在晚期被诊断出来.
目前的治疗方法,包括免疫检查点抑制剂和CAR-T疗法,由于T细胞透和持久性不足,其疗效有限.
需要新的策略来增强OC瘤微环境中的T细胞功能.

研究的目的:

开发一种针对CA125.5的卵巢癌的新型采用T细胞疗法.
为了增强在OC瘤微环境中的T细胞持久性和贩运.
为了评估双重准化学受体的协同抗瘤活性.

主要方法:

构建了一种新的CA125向化学受体 (CR),使用中素-CA125结合基因和4-1BB/CD3ζ信号碎片.
使用4H11抗体开发了一种向CA125的仿真抗原受体 (CAR).
电穿孔的CR和CAR编码RNA进入T细胞,并评估了体外和体外的抗瘤活性.

主要成果:

与单受体T细胞相比,共同表达CR和CAR的T细胞对卵巢癌细胞的杀死能力更强.
在瘤相互作用时,CR和CAR T细胞表现出激活标记和细胞因子释放的增加.
同时表达CR和CART细胞有效控制了瘤生长,并延长了小鼠模型中的存活时间.
转录基因组测序表明,同表达T细胞的存活率和细胞毒性有所提高.

结论:

同时通过CR和CAR准CA125,协同增强卵巢癌细胞的杀死.
这种双重准的方法有望改善卵巢癌治疗的治疗结果.
开发的CR-T和CAR-T细胞组合代表了卵巢癌免疫治疗的有前途的新战略.

关键词:

CA125 CA125 CA125 CA125 是一家在美国的公司.化学抗原受体 (CAR) 是一种化学受体 (CR) 是一种化学受体.梅索他林是其中一种.卵巢癌是发生在卵巢中的癌症.

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