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嵌合抗原受体修饰的T细胞治疗恶性血液系统疾病

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发表于 2016-1-28 19:26:42 | 显示全部楼层 |阅读模式
Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies.
On July 1, 2014, the United States Food and Drug Administration granted 'breakthrough therapy' designation to CTL019, the anti-CD19 chimeric antigen receptor T-cell therapy developed at the University of Pennsylvania. This is the first personalized cellular therapy for cancer to be so designated and occurred 25 years after the first publication describing genetic redirection of T cells to a surface antigen of choice. The peer-reviewed literature currently contains the outcomes of more than 100 patients treated on clinical trials of anti-CD19 redirected T cells, and preliminary results on many more patients have been presented. At last count almost 30 clinical trials targeting CD19 were actively recruiting patients in North America, Europe, and Asia. Patients with high-risk B-cell malignancies therefore represent the first beneficiaries of an exciting and potent new treatment modality that harnesses the power of the immune system as never before. A handful of trials are targeting non-CD19 hematological and solid malignancies and represent the vanguard of enormous preclinical efforts to develop CAR T-cell therapy beyond B-cell malignancies. In this review, we explain the concept of chimeric antigen receptor gene-modified T cells, describe the extant results in hematologic malignancies, and share our outlook on where this modality is likely to head in the near future.
嵌合抗原受体修饰的T细胞治疗恶性血液系统疾病
201471日,美国食品药品监督管理局对CTL019疗法,即宾夕法尼亚大学研发的靶向CD19 的嵌合抗原受体修饰的T细胞疗法授予了“突破性的疗法”称号。这是癌症的第一次的个性化疗法,距离第一次公开描述利用基因修饰介导T细胞选择性识别癌症细胞表面抗原有25年。目前同行评审的抗CD19重定向T细胞的临床试验结果有超过100例患者,并对许多患者的初步结果已提交。在去年,将近30个靶向CD19嵌合抗原受体的临床试验正在积极的招募患者,地区包括美国、欧洲和亚洲。患有高风险的B细胞恶性肿瘤患者因此代表着第一批受益者,之前从未有的利用免疫系统的力量的一种新的治疗方式。少数试验的目标是非靶向CD19的血液肿瘤和实体瘤,代表发展CAR-T细胞治疗B细胞恶性肿瘤之外的临床前研究工作的巨大的先锋。在这篇综述中,我们解释了嵌合抗原受体基因修饰细胞的概念,描述了目前血液系统恶性肿瘤的研究结果并分享CAR-T的前景,这种方式是可能在不久的将来具有重大突破。
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