Université Paris Cité, CNRS, INSERM, Equipe Labellisée Ligue Contre le Cancer, Institut Cochin, INSERM U1016, 22 rue Méchain, F-75014, Paris, France.
Invectys, Paris, France.
Semin Immunopathol. 2023 Mar;45(2):229-239. doi: 10.1007/s00281-023-00983-7. Epub 2023 Jan 23.
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.
嵌合抗原受体 (CAR) 表达 T 细胞的过继转移在对抗晚期 B 细胞恶性肿瘤方面显示出显著的临床疗效。尽管如此，CAR T 细胞领域目前仍面临着几个重大挑战。特别是，CAR T 细胞策略在靶向实体瘤时尚未产生有利的临床反应。在这种情况下，了解限制基于 T 细胞的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谱分析。这些方法对于确定决定 T 细胞增殖和扩增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，并与靶细胞形成有效的共轭物。结合创新的临床前模型的先进成像技术代表了揭示 CAR T 细胞动力学的有前途的工具。在这篇综述中，我们将讨论实时成像显微镜获得的关于工程 T 细胞生物学的最新结果。这些基于成像的研究提出了一些重要概念，例如 CAR T 细胞的多重杀伤潜力。最后，我们将强调成像技术与其他工具相结合如何解决工程 T 细胞领域中仍未解决的问题。
