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Heba Samaha^1,2,3,4, Antonella Pignata^2,3,4, Kristen Fousek^2,3,4,5

¹Children's Cancer Hospital Egypt-57357, Cairo, Egypt.

|September 7, 2018

概括

研究人员开发了一种新型的指导系统 (HS),以改善T细胞供应用于脑癌免疫治疗. 该系统针对癌细胞的激活白细胞粘附分子 (ALCAM),增强T细胞透和抗瘤活性.

科学领域:

免疫学
神经瘤学
细胞生物学

背景情况:

针对脑瘤的有效T细胞免疫疗法受到T细胞透到瘤组织中的挑战的阻碍.
在炎症条件下,内皮细胞对ICAM1和VCAM1进行免疫细胞外流调节,但脑癌内皮细胞对这些进行降低调节,以逃避免疫识别.
癌细胞内皮上调激活白细胞粘附分子 (ALCAM),成为免疫细胞的潜在目标.

研究的目的:

开发一种战胜脑癌内皮的免疫逃避机制的策略.
设计一种增强T细胞传递和透到脑瘤的系统.
提高T细胞免疫治疗脑癌的疗效.

主要方法:

通过重新设计ALCAM连接体CD6来开发ALCAM受限的定位系统 (HS).
通过使T细胞对癌症内皮的低水平ICAM1敏感,HS促进了T细胞初始结到ALCAM和二次粘附波.
在静脉注射后对人工细胞毒性T细胞透和抗瘤活性进行评估.

主要成果:

通过创建必要的粘附力, 设计的定位系统成功地调节了T细胞从血液中捕获.
人工合成的细胞毒性T细胞已经强烈地透到脑癌中.
在接受治疗的大脑癌症模型中观察到显著的抗瘤活性.

结论:

一种针对ALCAM的新型分子已经开发出来,专门将T细胞传递给脑癌.
这种方法克服了癌症内皮的免疫逃避,并增强了T细胞的透.
开发的系统有望提高T细胞免疫疗法的疗效.

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