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实现基于从诊断瘤活检中高通量TCR发现的下一代工程TCR-T疗法

Thomas Kuilman¹, Deborah S Schrikkema², Jules Gadiot²

¹Neogene Therapeutics, A member of the AstraZeneca Group, Amsterdam, The Netherlands. thomas.kuilman@astrazeneca.com.

Nature communications

|January 14, 2025

概括

这项研究引入了一个新的平台,用于从活检中识别瘤特异性T细胞受体 (TCR) 基因. 这一进展旨在改善各种固体癌症的采用细胞疗法,包括黑色素瘤和结直肠癌.

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:

使用瘤透淋巴细胞 (TIL) 的采用细胞疗法对固体癌症有希望,但受到TIL可访问性和功能的限制.
识别瘤特异性T细胞受体 (TCR) 对于增强工程T细胞疗法至关重要.

研究的目的:

开发一个有效的平台,从诊断瘤活检中识别瘤特异性TCR基因.
为了使工程T细胞疗法在更广泛的癌症中使用.

主要方法:

使用基因查方法检测具有高灵敏度和特异性的抗原反应性TCR.
高复杂性的TCR库与多重抗原库进行了选,以确定HLA类I和II受限制的TCR.
该平台在黑色素瘤和微卫星稳定的结直肠癌样本上进行了测试.

主要成果:

该平台有效地识别瘤特异性TCR基因,即使是来自非可行的冷核心针活检.
成功确定了HLA类I和II限制的TCR.
从黑色素瘤和低瘤突变负担结直肠癌样本中确定了新抗原特异性TCR.

结论:

开发的平台展示了用于工程T细胞治疗的TCRs识别的泛癌症潜力.
这项技术可以克服TIL可访问性和功能方面的局限性,扩大采用细胞治疗的应用.
该平台对多重抗原选多样化的TCR库的能力为TCR发现提供了一种敏感和特定的方法.

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