Sadelain Michel, Rivière Isabelle, Riddell Stanley
Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Nature. 2017 May 24;545(7655):423-431. doi: 10.1038/nature22395.
Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape. Advances in the selection of optimal T cells, genetic engineering, and cell manufacturing are poised to broaden T-cell-based therapies and foster new applications in infectious diseases and autoimmunity.
基因工程改造的T细胞是强大的新型药物,为癌症患者带来了治愈的希望。嵌合抗原受体(CAR)是一类可重新编程淋巴细胞特异性和功能的合成受体。靶向CD19的CAR在B细胞恶性肿瘤中已显示出显著疗效。从原理上讲,工程化T细胞适用于多种癌症,但仍需进一步取得进展以确定合适的靶抗原、克服免疫抑制性肿瘤微环境、降低毒性并防止抗原逃逸。在最佳T细胞选择、基因工程和细胞制造方面的进展有望拓宽基于T细胞的疗法,并在传染病和自身免疫性疾病中催生新的应用。
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