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利用T细胞耗尽和细胞分裂来分离患者衍生的瘤特异性TCR

Francesco Manfredi¹, Lorena Stasi¹, Silvia Buonanno¹

¹IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit, via Olgettina 60, Milan 20132, Italy.

Science advances

|December 1, 2023

概括

研究人员在干细胞移植后研究了TAA特异性T细胞. 他们发现这些细胞往往耗尽,但可以被利用来开发用于癌症免疫治疗的新型T细胞疗法.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
移植医学移植医学

背景情况:

全基性造血干细胞移植 (HSCT) 是血液恶性瘤的关键疗法.
了解HSCT后的T细胞动态对于改善移植对抗白血病效应和减少复发至关重要.
瘤相关抗原 (TAA) 是免疫媒介癌症疗法的点.

研究的目的:

为了研究TAA特异性T细胞在HSCT后的频率,表型和功能.
探索这些T细胞在开发新型癌症免疫疗法的潜力.
从耗尽的T细胞中识别T细胞受体 (TCR) 的特异性,用于治疗应用.

主要方法:

在39名HSCT患者的淋巴细胞群体长度分析1年.
TAA特异性T细胞的表型和功能特征.
将TCR转移到基因组编辑的T细胞中,以评估细胞分解功能.
巨细胞和体芯片技术用于识别TCR特异性.

主要成果:

在90%的患者中检测到TAA特异性T细胞,但表现出有限的效应器功能和疲劳表型.
在复发的患者中积累的耗尽的干细胞记忆T细胞.
只有在TCR转移到健康的T细胞后,才能实现有效的癌症特异性细胞分解功能.
从耗尽的T细胞中确定了针对TAA和新型急性髓性白血病抗原的新型TCR.

结论:

在HSCT后,循环的TAA特异性T细胞往往已经耗尽,限制了它们的内在抗瘤活性.
利用耗尽的T细胞及其TCRs为开发基于T细胞的癌症免疫疗法提供了一个有希望的策略.
这种方法可以识别针对TAA和以前未被描述的白血病抗原的新型TCR.

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相关概念视频

Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.