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:Chimeric Antigen Receptor (CAR)-T Cell Therapy for Non-Hodgkin's Lymphoma.
Chimeric Antigen Receptor (CAR)-T Cell Therapy for Non-Hodgkin's Lymphoma.
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本文综述嵌合抗原受体(CAR)T细胞治疗非霍奇金淋巴瘤(NHL)的应用。NHL是一类淋巴组织异质性恶性肿瘤。尽管已有多种传统化疗和多药化疗方案,NHL患者预后仍不佳,促使人们采用CAR-T 细胞等突破性的个体化疗法。CAR-T 细胞是经工程化改造、表达CAR的T细胞;CAR使其能够特异性裂解表达所选肿瘤抗原的肿瘤细胞。CAR由细胞外抗体片段或靶蛋白结合结构域构成,并与T细胞常见的胞内活化信号基序相连。
总体而言,NHL的CAR-T 疗法旨在识别B细胞上普遍表达的细胞标志物,如CD19⁺、CD20⁺和CD22⁺。使用CAR-T 细胞的临床试验(如ZUMA-7和TRANSFORM)相较标准治疗显示出令人鼓舞的结果,最终促成美国FDA批准其用于复发/难治性NHL。尽管CAR-T 治疗NHL取得成功,仍存在不良反应以及肿瘤外在和内在耐药机制等挑战,导致疗效未达最佳。
总体而言,CAR-T 疗法改善了NHL患者的临床结局,并为其未来应用带来了希望。
This review focuses on the use of chimeric antigen receptor (CAR)-T cell therapy to treat non-Hodgkin's lymphoma (NHL), a classification of heterogeneous malignant neoplasms of the lymphoid tissue. Despite various conventional and multidrug chemotherapies, the poor prognosis for NHL patients remains and has prompted the utilization of groundbreaking personalized therapies such as CAR-T cells. CAR-T cells are T cells engineered to express a CAR that enables T cells to specifically lyse tumor cells with extracellular expression of a tumor antigen of choice.
A CAR is composed of an extracellular antibody fragment or target protein binding domain that is conjugated to activating intracellular signaling motifs common to T cells. In general, CAR-T cell therapies for NHL are designed to recognize cellular markers ubiquitously expressed on B cells such as CD19 + , CD20 + , and CD22 + .
Clinical trials using CAR-T cells such as ZUMA-7 and TRANSFORM demonstrated promising results compared to standard of care and ultimately led to FDA approval for the treatment of relapsed/refractory NHL. Despite the success of CAR-T therapy for NHL, challenges include adverse side effects as well as extrinsic and intrinsic mechanisms of tumor resistance that lead to suboptimal outcomes.
Overall, CAR-T cell therapies have improved clinical outcomes in NHL patients and generated optimism around their future applications.
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