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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Practical aspects of CAR-T cell therapy.
Practical aspects of CAR-T cell therapy.
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嵌合抗原受体(CAR)T细胞治疗在血液系统恶性肿瘤治疗中的地位逐渐确立。目前,捷克共和国已批准3种自体抗CD19 CAR-T 细胞产品,用于治疗特定复发性B细胞非霍奇金淋巴瘤和急性B淋巴细胞白血病。其他临床试验正在评估靶向其他肿瘤特异性抗原的CAR-T 疗法。预计其中部分产品将在不久的将来获批用于其他血液肿瘤诊断。CAR-T 细胞疗法的制备和管理流程已得到优化。欧洲血液和骨髓移植学会以及美国移植与细胞治疗学会依据数年积累的宝贵经验,更新了CAR-T 治疗早期毒性的管理建议。然而,晚期毒性仍是问题。接受这一高度特异性治疗的患者必须进行长达数十年的随访。研究者已投入大量工作开发疗效更高、毒性更低的新型CAR构建体。通用异基因T细胞表达可结合肿瘤特异性抗原的CAR,有望显著提高这种原本非常昂贵治疗的可及性。
本文综述自体CAR-T 淋巴细胞的制备和给药。
Chimeric antigen receptor (CAR) T cell therapy has been gradually building its position in the treatment of hematological malignancies. Currently, there are three types of autologous anti-CD19 CAR-T cells approved for the treatment of selected relapsed B cell non-Hodgkins lymphomas and acute B-lymphoblastic leukemia in the Czech Republic. Additional clinical trials are ongoing to evaluate CAR-T cell therapy that targets other tumor-specific antigens. It is expected that some of these CAR-T cells will be approved for the treatment of other hemato-oncological dia-gnoses in the near future. Manufacturing and management of CAR-T cell therapy have been optimized. European Society for Blood and Marrow Transplantation and American Society for Transplantation and Cellular Therapy have updated their recommendations for the management and treatment of early CAR-T cell toxicity based on valuable experience gained during several years. Nevertheless, late toxicity remains an issue. It is crucial for patients undergoing this highly specific therapy to stay in follow-up for several decades. Intensive research and development have been devoted to manufacturing new CAR constructs with higher efficacy and lesser toxicity. A significant improvement in the availability of this, otherwise very expensive treatment, is expected from universal allogeneic T cells that will express CAR binding to tumor-specific antigen.
This review is focused on the preparation and administration of autologous CAR-T lymphocytes.
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