肿瘤细胞治疗研究
英文原题：Biomarker-empowered precision navigation of CAR-T cell therapy.
这些发现支持从单个候选标志物转向整合性的纵向框架，以指导精准CAR-T治疗，并进一步提高疗效、持久性和安全性。
CAR-T 细胞疗法已经彻底改变了复发或难治性血液系统恶性肿瘤的治疗，并仍在临床应用中不断推进。然而，其更广泛的应用受到疗效异质性、缓解持久性有限、抗原阴性复发以及急性和迟发性毒性的制约。因此，生物标志物对于预测临床结局、优化产品设计、完善患者选择、评估早期反应以及监测毒性至关重要。在本综述中，我们总结了决定 CAR-T 疗效和安全性的关键生物学区室中的当前生物标志物：宿主来源因素，包括基线炎症特征、免疫组成和 T 细胞适应性；产品相关特征，如 CAR 结构、细胞亚群、代谢状态、扩增和持久性；肿瘤来源标志物，包括抗原表达、基因组特征、微小残留病、循环肿瘤 DNA 和肿瘤微环境。我们还概述了与主要 CAR-T 相关毒性相关的生物标志物。最后，我们讨论了高参数流式细胞术、单细胞多组学、细胞外囊泡和新型 CAR 平台如何推动生物标志物的发展。总体而言，这些发现支持从单个候选标志物转向整合性纵向框架，以指导精准 CAR-T 治疗并进一步改善疗效、持久性和安全性。
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed or refractory hematologic malignancies and continues to advance clinically. However, its broader application is hindered by heterogeneous efficacy, limited response durability, antigen-negative relapse, and both acute and delayed toxicities. Biomarkers are therefore critical for predicting clinical outcomes, optimizing product design, refining patient selection, evaluating early responses, and monitoring toxicities. In this review, we summarize current biomarkers across key biological compartments that determine CAR-T efficacy and safety: host-derived factors including baseline inflammatory profiles, immune composition, and T-cell fitness; product-related features such as CAR structure, cellular subsets, metabolic state, expansion, and persistence; tumor-derived markers including antigen expression, genomic characteristics, minimal residual disease, circulating tumor DNA, and tumor microenvironment. We also outline biomarkers associated with major CAR-T-related toxicities. Finally, we discuss how high-parameter flow cytometry, single-cell multi-omics, extracellular vesicles, and novel CAR platforms are advancing biomarker development. Collectively, these findings support a shift from individual candidate markers toward integrated longitudinal frameworks to guide precision CAR-T therapy and further improve efficacy, durability, and safety.
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