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嵌合抗原受体 T 细胞疗法治疗血液系统恶性肿瘤和实体瘤:临床数据现状、当前局限性和展望。

Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives.

机构信息

Allogeneic Stem Cell Transplantation Unit, Department of Hematology, CHU de Lille, 59037 Lille, France; UFR Médecine, université de Lille (Lille University), 59000 Lille, France.

Allogeneic Stem Cell Transplantation Unit, Department of Hematology, CHU de Lille, 59037 Lille, France; UFR Médecine, université de Lille (Lille University), 59000 Lille, France; LIRIC-Inserm U995, université de Lille, FHU Imminent, CHU de Lille, 59000, France.

出版信息

Curr Res Transl Med. 2017 Sep;65(3):93-102. doi: 10.1016/j.retram.2017.08.003.

Abstract

Progress in our understanding of basic immunology along with the advent of bioengineering technologies have made possible the production of human T-cells expressing Chimeric Antigen Receptors (CAR T-cells). These CAR T-cells are designed to target specific antigens presented by cancer cells. Once CARs are bound to these antigens, CAR T-cells get activated and can initiate potent anti-tumor effects. We will here overview the bioengineering advances which made possible the clinical application of CAR T-cell therapy. We will review the data to date regarding anti-CD19 CAR T-cell therapy for acute lymphoblastic leukemia, non-Hodgkin lymphomas, and chronic lymphocytic leukemia. Besides CD19, CAR T-cells directed against the B-cell maturation antigen have also shown encouraging results to treat patients with refractory multiple myeloma. The more limited body of clinical research in the field of solid tumors will also be reviewed. Moreover, we will elaborate on the main toxicities of limitations of CAR T-cell therapy, namely cytokine release syndrome and neurotoxicity. While enjoying an undeniable hype, CAR T-cell therapy bears significant limitations. We will conclude by exposing the possible approaches to make CAR T-cells safer and more efficient beyond the CD19 target.

摘要

随着基础免疫学研究的进展和生物工程技术的出现,表达嵌合抗原受体(CAR T 细胞)的人类 T 细胞的生产成为可能。这些 CAR T 细胞旨在针对癌细胞表面呈现的特定抗原。一旦 CAR 与这些抗原结合,CAR T 细胞就会被激活,并能够引发有效的抗肿瘤作用。在这里,我们将概述使 CAR T 细胞疗法能够临床应用的生物工程进展。我们将回顾迄今为止有关抗 CD19 CAR T 细胞疗法治疗急性淋巴细胞白血病、非霍奇金淋巴瘤和慢性淋巴细胞白血病的数据。除了 CD19,针对 B 细胞成熟抗原的 CAR T 细胞也显示出令人鼓舞的结果,可用于治疗难治性多发性骨髓瘤患者。我们还将回顾实体肿瘤领域更为有限的临床研究。此外,我们将详细阐述 CAR T 细胞疗法的主要毒性和局限性,即细胞因子释放综合征和神经毒性。虽然 CAR T 细胞疗法受到了不可否认的关注,但它也存在显著的局限性。我们将通过探讨除 CD19 靶点之外使 CAR T 细胞更安全、更有效的可能方法来结束本文。

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