CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Molecular Insights and Novel Therapies for Lymphoproliferative Disorders.
Molecular Insights and Novel Therapies for Lymphoproliferative Disorders.
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血液系统恶性肿瘤涵盖多种相对罕见的癌症,生物学和临床特征各异,可影响各年龄段人群,但部分亚型更常见于特定年龄范围。新一代测序技术的进步极大增进了对这些疾病分子和遗传基础的认识,表观遗传、转录和蛋白质组分析则进一步阐明了其发病机制。这些进展推动了淋巴瘤分类和治疗的发展。纳入临床相关分子靶点的新分类框架,为多种靶向药物开辟了道路,各药物旨在利用恶性细胞的特定弱点;干细胞移植仍可使符合条件的患者获得治愈机会,且安全性随时间不断提高。CAR-T 细胞疗法已拓展至多种血液系统肿瘤适应证,使既往治疗选择已耗尽的患者获得持久缓解。双特异性抗体则通过将患者自身T细胞重新引导至肿瘤细胞,进一步拓展免疫治疗格局,并提供易于获得的替代方案,克服CAR-T 制造的许多实际局限。联合应用这些策略,已从根本上改变血液肿瘤治疗的可及目标,使许多患者实现长期缓解成为现实。本综述旨在概述淋巴瘤和白血病的核心分子机制,评估目前获批的治疗选择,讨论可能改变临床实践的重要在研临床试验,并探讨为经谨慎筛选患者采用无化疗方案的前景。
Hematological malignancies encompass a broad spectrum of relatively rare cancers with diverse biological and clinical characteristics that are capable of affecting individuals across all age groups, though certain subtypes show a predilection for specific age ranges. Advances in next-generation sequencing have greatly enhanced our understanding of the molecular and genetic basis of these diseases, while epigenetic, transcriptional, and proteomic analyses have further clarified their pathogenesis. These developments have shaped the classification and treatment of lymphoma. Updated classification frameworks which include the identification of clinically relevant molecular targets have opened the door to a number of targeted agents, each designed to exploit specific vulnerabilities within malignant cells, while stem cell transplantation continues to offer curative potential for eligible patients, with improving safety profiles over time.
CAR-T-cell therapy has been extended to multiple blood cancer indications, achieving lasting remissions in patients with previously exhausted treatment options. Bispecific antibodies have further broadened the immunotherapy landscape by redirecting the body's own T cells against tumor cells, offering a readily available alternative that overcomes many of the practical limitations associated with CAR-T-cell production.
The ability to combine these strategies has fundamentally changed what is achievable in blood cancer treatment, with long-term remission now a realistic goal for many patients. This review seeks to outline the core molecular mechanisms underlying lymphoma and leukemia, evaluate currently approved treatment options, discuss significant ongoing clinical trials with practice-changing potential, and explore the prospect of chemotherapy-free approaches in carefully selected patient groups.
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