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基于CD28的非超激素双信号T细胞参与者准非超激素

Tianran Chen¹, Ying Wang¹, Xiaotong Chen¹

¹The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital & Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China.

Journal for immunotherapy of cancer

|January 20, 2026

概括

这项研究开发了针对 KK-LC-1 固体瘤的新型双信号T细胞参与剂. 在临床前模型中,将KK-LC-1×CD28与PD-1×CTLA-4双特异抗体结合起来,协同增强了抗瘤疗效.

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:

双特异性T细胞参与者表现有前途,但面临诸如单信号激活的T细胞活力等挑战.
CD28协同刺激增强T细胞功能和抗瘤功效,非超级激素的方法将毒性降到最低.
基塔-九州肺癌抗原-1 (KK-LC-1) 是一种有前途的癌症丸抗原免疫治疗标.

研究的目的:

开发一种双信号T细胞参与策略,使用CD28协同刺激准KK-LC-1.
评估单独和组合疗法中KK-LC-1-向的T细胞参与剂的抗瘤疗效.

主要方法:

使用菌体显示技术为KK-LC-1和CD28目标设计了两个T细胞参与者 (KK-LC-1×CD3和KK-LC-1×CD28).
经过验证的结合活性和评估的生物活性以及 in vitro 和 in vivo 的抗瘤疗效.

主要成果:

工程设计的KK-LC-1×CD3和KK-LC-1×CD28接触器显示出高的结合亲和力.
与单独治疗相比,与参与者联合使用增加了T细胞激活和抗瘤疗效.
组合疗法抑制了瘤生长,增强了内CD8+和CD4+T细胞的透,并延长了中位生存期.

结论:

验证了针对固体瘤的KK-LC-1-向双信号T细胞参与策略的可行性.
在临床前研究中,与PD-1×CTLA-4双特异性抗体结合时,证明了抗瘤功效的协同增强.

关键词:

双特异性T细胞参与者 - BiTE 组合疗法是一种联合疗法.固体瘤是一个固体瘤.

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