用于评估经收养转移的工程化 TCR T 细胞体内多功能性的快速方法。

IF 4.1 Q2 IMMUNOLOGY
Immunotherapy advances Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI:10.1093/immadv/ltae007
Anthony T Tan, Shou Kit Hang, Nicole Tan, Thinesh L Krishnamoorthy, Wan Cheng Chow, Regina Wanju Wong, Lu-En Wai, Antonio Bertoletti
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引用次数: 0

摘要

导言:嵌合抗原和T细胞受体(TCR)T细胞免疫疗法的临床疗效归功于它们在体内增殖和存活的能力。由于工程 T 细胞与目标肿瘤或其环境的相互作用可能会抑制它们的功能,因此不仅在采用性转移之前,而且在采用性转移之后都应该对它们的功能进行鉴定:为了实现这一目标,我们对最近开发的严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)快速全血 T 细胞检测方法进行了改良,以刺激小量全血(体外细胞纯化)中的工程 TCR T 细胞。作为概念验证,我们用这种方法对两名原发性乙型肝炎病毒(HBV)相关肝细胞癌患者进行了纵向研究,这两名患者接受了多剂量递增的瞬时功能性 mRNA 工程 HBV-TCR T 细胞输注:结果:我们发现,用与特异性 HBV-TCR 识别的表位相对应的多肽对全血进行简单脉冲,仅在 HBV-TCR T 细胞治疗后才会引起这两名患者分泌 Th1 细胞因子,而在治疗前则不会。细胞因子的分泌量也与输注剂量有关:讨论:这些研究结果支持全血细胞因子释放检测法在监测收养性转移后工程 T 细胞产品的体内功能和数量方面的实用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A rapid method to assess the in vivo multi-functionality of adoptively transferred engineered TCR T cells.

Introduction: The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies is attributed to their ability to proliferate and persist in vivo. Since the interaction of the engineered T cells with the targeted tumour or its environment might suppress their function, their functionality should be characterized not only before but also after adoptive transfer.

Materials and methods: We sought to achieve this by adapting a recently developed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid whole blood T cell assay to stimulate engineered TCR T cells in small volumes of whole blood (<1 ml) without in vitro cellular purification. As a proof-of-concept, we used this method to longitudinally study two patients with primary Hepatitis B Virus (HBV)-related hepatocellular carcinoma who received multiple dose-escalating infusions of transiently functional mRNA-engineered HBV-TCR T cells.

Results: We demonstrated that a simple pulsing of whole blood with a peptide corresponding to the epitope recognized by the specific HBV-TCR elicited Th1 cytokine secretion in both patients only after HBV-TCR T cell treatment and not before. The amount of cytokines secreted also showed an infusion-dose-dependent association.

Discussions: These findings support the utility of the whole blood cytokine release assay in monitoring the in vivo function and quantity of engineered T cell products following adoptive transfer.

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