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T细胞介导的嵌合抗原受体选择性对抗T细胞肿瘤

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发表于 2016-1-11 20:22:47 | 显示全部楼层 |阅读模式
A T-cell–directed chimeric antigen receptor for the selective treatment of T-cell malignancies
Options for targeted therapy of T-cell malignancies remain scarce. Recent clinical trials demonstrated that chimeric antigen receptors (CARs) can effectively redirect T lymphocytes to eradicate lymphoid malignancies of B-cell origin. However, T-lineage neoplasms remain a more challenging task for CAR T cells due to shared expression of most targetable surface antigens between normal and malignant T cells, potentially leading to fratricide of CAR T cells or profound immunodeficiency. Here, we report that T cells transduced with a CAR targeting CD5, a common surface marker of normal and neoplastic T cells, undergo only limited fratricide and can be expanded long-term ex vivo. These CD5 CAR T cells effectively eliminate malignant T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma lines in vitro and significantly inhibit disease progression in xenograft mouse models of T-ALL. These data support the therapeutic potential of CD5 CAR in patients with T-cell neoplasms.
T细胞介导的嵌合抗原受体选择性对抗T细胞肿瘤
靶向治疗T细胞肿瘤的方案仍然很少。最近的临床试验证实了嵌合抗原受体(CARs)能够有效的对抗T 淋巴细胞来消除B淋巴细胞来源的恶性肿瘤。然而,T 细胞系肿瘤对于使用CAR-T 细胞治疗仍然是一个大的挑战,因为CAR-T细胞靶向的目标在正常细胞和恶性T淋巴细胞表面共同表达,从而导致CAR-T 细胞自相残杀或者免疫缺陷。在这篇文章中,我们报道了使用转导了CD5T细胞,CD5是一个在正常组织和肿瘤T细胞表面都有表达的表面标记物,CD5 CAR-T细胞能够有一个有限的自相残杀能力,但是在体外能够有一个长效的扩增能力。体外试验中,这些 CD5 CAR-T 细胞能够有效消除恶性 T 细胞以及急性淋巴细胞白血病 (T-ALL) T 细胞淋巴瘤,并显著抑制异种移植小鼠模型的 T-ALL病程。这些数据说明了利用CD5 CAR-T细胞具有对抗T淋巴细胞白血病的潜能。
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