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Updated: Jan 18, 2026

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针对TP53突变相关新抗原的双特异性抗体和CAR T细胞表现出不一致的亲和力要求

Sarah R DiNapoli^1,2,3, Katharine M Wright^2,4,5, Brian J Mog^1,2,3,6

¹Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

The Journal of clinical investigation

|January 16, 2026

概括

增加向分子对突变相关新抗原 (MANAs) 的亲和力可以增强双特异性抗体疗法,但会损害CAR T细胞的功能. 这一发现影响了新型癌症免疫疗法的设计.

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:

突变相关的新抗原 (MANAs) 是免疫治疗的特定癌症点.
癌细胞上的低MANA密度限制了治疗效果.
双特异性抗体和CAR T细胞可以准MANA来激活T细胞.

研究的目的:

调查是否增加针对p53 R175H MANA的单链可变片段 (scFv) 的亲和力可以提高治疗效果.
为了确定增加scFv亲和力对双特异抗体和CAR T细胞功能的影响.

主要方法:

菌体生物扫描和硫酸盐化被用来识别更高亲和度的H2 scFv变体.
更高亲和度的scFvs被纳入双特异性抗体和CAR T细胞结构 (CD28z,CD3γ,TCR).
在老鼠异种移植模型中评估了癌细胞杀死和瘤控制.

主要成果:

增加双特异性抗体亲和力增强了癌细胞杀死和瘤控制,而不会影响特异性.
相反,无论CAR格式如何,增加了CAR T细胞亲和力,降低了T细胞激活和抗癌功能.
观察到亲和力增强对双特异性抗体和CAR T细胞的影响之间存在显著的对比.

结论:

向分子的增强亲和力对双特异性抗体和CAR T细胞产生差异性影响.
优化亲和力对于开发针对低密度MANA的有效免疫疗法至关重要.
这些发现为未来MANA向癌症治疗的合理设计提供了关键的见解.

关键词:

癌症免疫疗法癌症免疫疗法免疫学免疫学免疫学免疫治疗是一种免疫疗法.在瘤学瘤学.在T细胞,T细胞.

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