血液肿瘤CAR-T细胞治疗的现状与挑战 |
| |
引用本文: | 康云,梅恒,胡豫.血液肿瘤CAR-T细胞治疗的现状与挑战[J].中国肿瘤临床,2023,50(1):49-54. |
| |
作者姓名: | 康云 梅恒 胡豫 |
| |
作者单位: | 华中科技大学同济医学院附属协和医院血液科,湖北省肿瘤疾病细胞治疗临床医学研究中心(武汉市430022) |
| |
基金项目: | 本文课题受科技部重点研发计划项目(编号:2019YFC1316200)和湖北省自然科学基金项目(编号:2020CFA065)资助 |
| |
摘 要: | 过继性细胞免疫疗法(adoptive cellular immunotherapy,ACI)是药物开发中一种全新模式,目前已具备在肿瘤疾病中带来临床益处的明确证据。其中嵌合抗原受体修饰的T细胞(chimeric antigen receptor-modified T cells,CAR-T)疗法利用基因工程技术重编程T细胞,使其具备非主要组织相容性抗原复合物(major histocompability complex,MHC)限制性的靶向结合并杀伤肿瘤细胞的能力,并在急性B淋巴细胞性白血病(B-cell acute lymphoblastic leukemia,B-ALL)、非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)、多发性骨髓瘤(multiple myeloma,MM)患者中展现出显著的缓解率,为难治复发性血液肿瘤疾病提供了治愈希望,因此多项商品化CAR-T产品也获批应用于临床,开拓了肿瘤免疫治疗的新时代。然而,细胞因子释放综合征(cytokine release syndrome,CRS)、免疫效应细胞相关神经毒性综合征(immune effector cell-associated neurotoxicity syndrome,ICANS)和其他并发症的发生是其应用的安全性挑战,并且部分患者发生CAR-T治疗无效或复发,需要提出优化CAR-T细胞疗法的新策略,在不同水平强化肿瘤清除作用,以确保安全性和有效性。本文对血液肿瘤领域的CAR-T细胞疗法临床研究进展进行综述,并归纳了下一代CAR-T细胞疗法面临的主要挑战,为拓展CAR-T细胞基础研究及临床转化研究方向提供思路。
|
关 键 词: | 血液恶性肿瘤 嵌合抗原受体T细胞 过继性细胞免疫治疗 抗原逃逸 |
收稿时间: | 2022-10-05 |
Current status and challenges in chimeric antigen receptor-modified T cell immunotherapies for hematological malignancies |
| |
Institution: | Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan 430022, China |
| |
Abstract: | Adoptive cellular immunotherapy, a novel treatment paradigm, has demonstrated clinical success in oncological diseases. In chimeric antigen receptor-modified T cell (CAR-T) therapy, genetic engineering techniques reprogram T cells to enable them to target and eliminate tumor cells in a non major histocompability complex (MHC)-restricted manner. Significant disease remission rates were achieved in B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin’s lymphoma (NHL), and multiple myeloma (MM), providing patients with refractory and recurring hematological malignancies with opportunities to be cured. Therefore, several commercialized CAR-T products have received approval for clinical application, opening up a new era of tumor immunotherapy. Nevertheless, the development of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and other complications pose a threat to the application of CAR-T therapy. In addition, some patients develop resistance to CAR-T treatment; thus, new strategies to optimize CAR-T cell therapy are necessary to enhance eradication of tumor cells from various aspects. In this article, we provide an overview of the clinical research of CAR-T cell therapies in hematological malignancies and summarize the main challenges in future CAR-T cell therapy to provide insights to researchers on the development of CAR-T basic study and clinical translational research. |
| |
Keywords: | |
|
| 点击此处可从《中国肿瘤临床》浏览原始摘要信息 |
| 点击此处可从《中国肿瘤临床》下载免费的PDF全文 |
|