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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Advancements and expanding applications of CAR-T cell therapy.
Advancements and expanding applications of CAR-T cell therapy.
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CAR-T 细胞疗法已成为肿瘤学中一种变革性的治疗模式,在血液系统恶性肿瘤中展现出持久的临床疗效。近期研究已将其潜力从癌症拓展至免疫介导性疾病,包括多发性硬化症和系统性红斑狼疮等自身免疫性疾病,以及HIV和乙型肝炎等慢性病毒感染。本综述探讨了CAR-T 细胞的机制基础、旨在减轻移植物抗宿主病和宿主排斥的通用型和异体工程策略的进展,以及旨在绕过传统体外制造的新兴体内基因递送平台。我们进一步评估了安全性控制架构,包括逻辑门控和诱导型系统,并讨论了与可扩展性、生产标准化和长期免疫持久性相关的转化障碍。尽管基因组编辑、合成生物学和计算设计方面的技术创新持续完善CAR-T 平台,但重大的生物学和后勤挑战依然存在。对这些不断演变的策略进行批判性综合,对于区分渐进式优化与范式转变性进展,以及界定CAR为基础免疫治疗在肿瘤学和免疫介导性疾病中的未来轨迹,是必要的。
CAR T-cell therapy has become a transformative modality in oncology, demonstrating sustained clinical efficacy in hematologic malignancies. Recent investigations have expanded its potential beyond cancer to immune-mediated disorders, including autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus, as well as chronic viral infections including HIV and hepatitis B.
This review examines the mechanistic foundations of CAR-T cells, advances in universal and allogeneic engineering strategies designed to mitigate graft-versus-host disease and host rejection, and emerging in vivo gene-delivery platforms that aim to bypass conventional ex vivo manufacturing.
We further evaluate safety-control architectures, including logic-gated and inducible systems, and discuss translational barriers related to scalability, manufacturing standardization, and long-term immune durability. While technological innovations in genome editing, synthetic biology, and computational design continue to refine CAR-T platforms, substantial biological and logistical challenges remain.
A critical synthesis of these evolving strategies is necessary to distinguish incremental optimization from paradigm-shifting advances and to define the future trajectory of CAR-based immunotherapy across oncology and immune-mediated diseases.
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