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通过T细胞激活双特异性抗体逆转内皮细胞无能

Márcia Gonçalves^1,2, Karsten M Warwas^1,2,3, Marten Meyer^1,2,3

¹Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

|January 8, 2025

概括

针对内皮细胞 (EC) 和T细胞的双特异性抗体增强了T细胞透到瘤中的作用. 这些工程抗体逆转EC anergy,促进T细胞激活和迁移以改善癌症免疫疗法.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

减少附分子在瘤血管上的表达限制了T细胞透.
瘤内皮细胞 (ECs) 经常表现出无能状态,阻碍T细胞相互作用.
双特异性抗体 (bsAbs) 提供了一种桥梁T细胞和瘤ECs的策略.

研究的目的:

设计和评估双特异性抗体,以增强T细胞粘附和超内皮细胞迁移.
通过使用新的bsAbs. 来研究T细胞和瘤ECs的激活.
评估bsAbs在克服免疫抑制瘤微环境方面的潜力.

主要方法:

工程重组T细胞刺激抗VEGFR2-抗CD3和共刺激抗TIE2-抗CD28或抗PD-L1-抗CD28 bsAbs.
利用人类静脉内皮细胞 (HUVECs) 作为性瘤ECs的模型.
进行了共同培养试验,细胞因子释放测量,粘附分子上调分析和跨井迁移试验.

主要成果:

抗VEGFR2-抗CD3 bsAb增加了与HUVECs共同培养的T细胞结合和激活.
辅助刺激性bsAbs (anti-TIE2-anti-CD28或anti-PD-L1-anti-CD28) 增加了T细胞细胞因子的释放 (TNF-α,IFN-γ,IL-6).
从T细胞衍生的细胞因子在HUVEC上调节了粘附分子 (E-selectin,ICAM1,VCAM1),增强了T细胞迁移和细胞毒性活性.

结论:

工程T细胞参与的bsAbs可以在体外逆转静止ECs的能量.
结合治疗EC向和辅助刺激的bsAbs可以改善T细胞的迁移和功能.
这种方法有望通过克服血管障碍来增强基于T细胞的癌症免疫疗法.

关键词:

在T细胞激活过程中,两种特异性的抗体.超内皮细胞迁移的跨内皮细胞迁移.瘤免疫疗法免疫疗法瘤血管的向是针对瘤的血管.

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