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CAR-T 细胞:一种癌症免疫治疗

英文原题:Chimeric antigen receptor T cell: A cancer immunotherapy.

PubMed 2022/05/01(内容时间) Indian J Pharmacol Q4 · IF 1.2(JCR 2025)

研究概要

在当前这十年中,靶向药物治疗一直是癌症治疗的典范。

中文摘要

过去十年,靶向药物治疗已成为癌症治疗的典型代表。例如,酪氨酸激酶受体抑制剂Imatinib和人表皮生长因子受体2/neu抑制剂Trastuzumab,已广泛开发并分别用于慢性髓性白血病和乳腺癌。免疫疗法的近期进展之一是过继细胞转移(ACT)。多种ACT免疫疗法正在研发,而CAR-T 细胞疗法的临床开发目前最为先进。CAR是经过改造的受体,可将特异性和应答能力赋予免疫细胞,增强其识别癌细胞的能力。CAR-T制备时,通过单采从患者血液中收集T细胞,将特定抗原相关DNA导入采集的T细胞,使其表面表达CAR。受体表达后,在富集培养基中扩增,再回输患者体内。输注后,CAR-T靶向并清除癌细胞。最初仅有两种靶向CD19的基因改造自体免疫疗法获批,即Tisagenlecleucel和Axicabtagene Ciloleucel,本文对此作详细讨论。近期又有两种药物获批,即同样靶向CD19的brexucabtagene ciloleucel和lisocabtagene maraleucel。CAR-T疗法已获批用于急性淋巴细胞白血病、慢性淋巴细胞白血病和淋巴瘤。CAR-T细胞持久性既关系疗效,也关系安全性,是其广泛应用的障碍。生长因子受体和分化簇分子是正在探索的癌症免疫治疗新靶点。

展开英文摘要原文

During present decade, targeted drug therapy has been the epitome for treatment of cancer. Drugs like Imatinib, a tyrosine kinase receptor inhibitor and Trastuzumab, an human epidermal growth factor receptor-2/neu inhibitor, has been developed and accepted widely for management of chronic myeloid leukaemia and breast cancer respectively. Recent development among the various immunotherapies is adoptive cell transfer (ACT). Research on development of various types of ACT immunotherapy is going on, but so far, Chimeric antigen receptors T cell therapy (CAR-T) has achieved the maximum advancement in terms of clinical development. CARs are the modified receptors that integrates specificity and responsiveness onto immune cells to enhance the recognition of cancer cells. For the CAR-T, the T cells are sequestered from a blood of a participant via apheresis. DNA of particular antigen is injected into harvested T cells to generate CARs on cell surface. Following surface manifestation of receptors, multiplication is carried out in enriched media followed by infusion into patient. After infusion, CAR-T cells targeted and exterminate the cancer cells. Initially, only two drugs targeting CD19 as genetically modified autologous immunotherapy has been approved in CAR-T therapy i.e., Tisagenlecleucel and Axicabtagene Ciloleucel, which are discussed in detail in current review. Recently two more drugs got approval i.e., brexucabtagene ciloleucel and lisocabtagene maraleucel, both are directed against CD19, similar to tisagenlecleucel. CAR-T cell therapy is approved for management of Acute Lymphoblastic Leukaemia, Chronic Lymphocytic Leukaemia and lymphoma. CAR-T cell persistence responsible for effectiveness and safety concerns are barriers for their wide application among patients. Growth factor receptors and cluster of differentiation are new drugs targets that are being explored as effective immunotherapy against cancers.

论文信息

作者
Singh S、Khasbage S、Kaur RJ、Sidhu JK、Bhandari B
第一作者单位
Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.India
通讯作者单位
Department of Physiology, Government Institute of Medical Sciences, Greater Noida, India.India
文献类型
综述
期刊
Indian journal of pharmacology2022 May-Jun
原文标识
PubMed 35848695 · DOI 10.4103/ijp.ijp_531_20