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引用次数: 0
摘要
嵌合抗原受体(CAR)T 细胞疗法的问世是治疗白血病、淋巴瘤和骨髓瘤等抗药性癌症的一个里程碑式的进步。然而,美国食品及药物管理局(FDA)对 CAR-T 细胞治疗后出现第二原发性恶性肿瘤(SPM)的报告进行调查后,出现了对长期安全性的担忧。本综述对转基因 T 细胞如何转化为 CAR+ SPM 进行了深入研究。它探讨了导致T细胞淋巴瘤发生的基因和分子途径、CAR T细胞持久性、干性和致癌风险之间的平衡,以及T细胞衰竭的权衡,这可能会限制疗效,但有可能降低淋巴瘤发生的风险。
The Fate(s) of CAR T-Cell Therapy: Navigating the Risks of CAR+ T-Cell Malignancy.
The introduction of chimeric antigen receptor (CAR) T-cell therapy represents a landmark advancement in treating resistant forms of cancer such as leukemia, lymphoma, and myeloma. However, concerns about long-term safety have emerged following an FDA investigation into reports of second primary malignancies (SPM) after CAR-T cell treatment. This review offers a thorough examination of how genetically modified T cells might transform into CAR+ SPM. It explores genetic and molecular pathways leading to T-cell lymphomagenesis, the balance between CAR T-cell persistence, stemness, and oncogenic risk, and the trade-off of T-cell exhaustion, which may limit therapy efficacy but potentially reduce lymphomagenesis risk. Significance: An FDA probe into 22 cases of second primary T-cell malignancies following CAR T-cell therapy stresses the need to investigate their origins. Few may arise from preexisting genetic and epigenetic alterations and those introduced during therapeutic engineering. Technological advances, regulatory oversight, and patient monitoring are essential to mitigate potential risks.
期刊介绍:
The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes.
The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence.
Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.