CAR T-cell behavior and function revealed by real-time imaging.

IF 7.9 2区 医学 Q1 IMMUNOLOGY Seminars in Immunopathology Pub Date : 2023-03-01 DOI:10.1007/s00281-023-00983-7
David Espie, Emmanuel Donnadieu
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引用次数: 6

Abstract

Adoptive transfer of T-cells expressing chimeric antigen receptors (CAR) has shown remarkable clinical efficacy against advanced B-cell malignancies. Nonetheless, the field of CAR T-cells is currently facing several major challenges. In particular, the CAR T-cell strategy has not yet produced favorable clinical responses when targeting solid tumors. In this context, it is of paramount importance to understand the determinants that limit the efficacy of T-cell-based immunotherapy. Characterization of CAR T-cells is usually based on flow cytometry and whole-transcriptome profiling. These approaches have been very valuable to determine intrinsic elements that condition T-cell ability to proliferate and expand. However, they do not take into account spatial and kinetic aspects of T-cell responses. In particular, in order to control tumor growth, CAR T-cells need to enter into the tumor, migrate within a complex tumor environment, and form productive conjugates with their targets. Advanced imaging techniques combined with innovative preclinical models represent promising tools to uncover the dynamics of CAR T-cells. In this review, we will discuss recent results on the biology of engineered T-cells that have been obtained with real-time imaging microscopy. Important notions have emerged from these imaging-based studies, such as the multi-killing potential of CAR T-cells. Finally, we will highlight how imaging techniques combined with other tools can solve remaining unresolved questions in the field of engineered T-cells.

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实时成像揭示CAR -t细胞的行为和功能。
表达嵌合抗原受体(CAR)的t细胞过继转移治疗晚期b细胞恶性肿瘤显示出显著的临床疗效。尽管如此,CAR - t细胞领域目前面临着几个主要挑战。特别是,CAR - t细胞策略在针对实体肿瘤时尚未产生良好的临床反应。在这种情况下,了解限制t细胞免疫疗法疗效的决定因素至关重要。CAR -t细胞的表征通常基于流式细胞术和全转录组分析。这些方法对于确定制约t细胞增殖和扩张能力的内在因素非常有价值。然而,它们没有考虑到t细胞反应的空间和动力学方面。特别是,为了控制肿瘤生长,CAR - t细胞需要进入肿瘤,在复杂的肿瘤环境中迁移,并与靶标形成生产性偶联物。先进的成像技术与创新的临床前模型相结合,代表了揭示CAR - t细胞动力学的有希望的工具。在这篇综述中,我们将讨论利用实时成像显微镜获得的工程t细胞生物学的最新结果。从这些基于成像的研究中出现了重要的概念,例如CAR - t细胞的多重杀伤潜力。最后,我们将强调成像技术如何与其他工具相结合,可以解决工程t细胞领域仍未解决的问题。
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来源期刊
Seminars in Immunopathology
Seminars in Immunopathology 医学-病理学
CiteScore
19.80
自引率
2.20%
发文量
69
审稿时长
12 months
期刊介绍: The aim of Seminars in Immunopathology is to bring clinicians and pathologists up-to-date on developments in the field of immunopathology.For this purpose topical issues will be organized usually with the help of a guest editor.Recent developments are summarized in review articles by authors who have personally contributed to the specific topic.
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