文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

嵌合抗原受体T细胞疗法治疗多发性骨髓瘤:前景与挑战

Chimeric antigen receptor T cell therapy in multiple myeloma: promise and challenges.

作者信息

Dhakal Binod, Hari Parameswaran N, Usmani Saad Z, Hamadani Mehdi

机构信息

BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.

Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Atrium Health, Charlotte, NC, 28204, USA.

出版信息

Bone Marrow Transplant. 2021 Jan;56(1):9-19. doi: 10.1038/s41409-020-01023-w. Epub 2020 Aug 7.


DOI:10.1038/s41409-020-01023-w
PMID:32770147
Abstract

Despite a sea change in the therapeutic landscape, multiple myeloma (MM), a cancer of antibody producing plasma cells, remains incurable requiring continued intervention for disease control. In this context, chimeric antigen receptor (CAR) T cell therapy has emerged as a promising immunotherapeutic approach with unprecedented results in heavily treated relapsed and/or refractory MM patients. Although B cell maturation antigen (BCMA) is the current lead target for CAR-T cell therapy in MM, several other antigenic targets are also being investigated. Relapses, however, are inevitable in spite of the promising early responses, and may be mediated by antigenic modulation, poor persistence and "immunostat" in tumor microenvironment. Akin to multi-agent chemotherapy, multi-targeted CAR-T antigens and combinatorial approaches are underway to overcome the resistance mechanisms. Further, CAR-T specific toxicity concerns such as cytokine release syndrome and neurotoxicity, as well as manufacturing time lag are other key challenges. Allogeneic CAR that offers "off-the-shelf" options, and mRNA transfected CAR are being developed to mitigate the access and safety issues. In this review we provide the comprehensive review of the most current clinical trial data for CAR-T in myeloma, challenges associated with this therapy and discuss its future in myeloma therapeutics.

摘要

尽管治疗格局发生了巨大变化,但多发性骨髓瘤(MM),一种产生抗体的浆细胞癌症,仍然无法治愈,需要持续干预以控制疾病。在这种背景下,嵌合抗原受体(CAR)T细胞疗法已成为一种有前途的免疫治疗方法,在经过大量治疗的复发和/或难治性MM患者中取得了前所未有的成果。虽然B细胞成熟抗原(BCMA)是目前MM中CAR-T细胞疗法的主要靶点,但其他几个抗原靶点也在研究中。然而,尽管早期反应很有希望,但复发是不可避免的,可能由抗原调节、持久性差和肿瘤微环境中的“免疫稳态”介导。与多药化疗类似,正在进行多靶点CAR-T抗原和联合方法来克服耐药机制。此外,CAR-T特异性毒性问题,如细胞因子释放综合征和神经毒性,以及生产时间延迟是其他关键挑战。提供“现货”选择的同种异体CAR和mRNA转染的CAR正在开发中,以缓解可及性和安全性问题。在这篇综述中,我们全面回顾了CAR-T治疗骨髓瘤的最新临床试验数据、与该疗法相关的挑战,并讨论了其在骨髓瘤治疗中的未来。

相似文献

[1]
Chimeric antigen receptor T cell therapy in multiple myeloma: promise and challenges.

Bone Marrow Transplant. 2021-1

[2]
Chimeric antigen receptor T-cell therapy for multiple myeloma.

Front Immunol. 2022

[3]
CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies.

Front Immunol. 2023

[4]
Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma.

Pharmacol Ther. 2022-4

[5]
Paving the Way toward Successful Multiple Myeloma Treatment: Chimeric Antigen Receptor T-Cell Therapy.

Cells. 2020-4-16

[6]
[CAR-T cells immunotherapy in multiple myeloma: Present and future].

Bull Cancer. 2021-10

[7]
Efficacy and Safety of CAR-T Therapy for Relapse or Refractory Multiple Myeloma: A systematic review and meta-analysis.

Int J Med Sci. 2021

[8]
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Mol Ther. 2019-4-8

[9]
Allogeneic Anti-BCMA CAR T Cells Are Superior to Multiple Myeloma-derived CAR T Cells in Preclinical Studies and May Be Combined with Gamma Secretase Inhibitors.

Cancer Res Commun. 2022-3

[10]
Anti-BCMA CAR T-cell therapy in multiple myeloma: can we do better?

Leukemia. 2019-11-28

引用本文的文献

[1]
Targets for CAR Therapy in Multiple Myeloma.

Int J Mol Sci. 2025-6-24

[2]
CD4+ CAR T-cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR T-cell therapy.

Blood Adv. 2024-7-9

[3]
Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma.

J Immunother Cancer. 2024-1-8

[4]
Nicotinamide-Expanded Allogeneic Natural Killer Cells with CD38 Deletion, Expressing an Enhanced CD38 Chimeric Antigen Receptor, Target Multiple Myeloma Cells.

Int J Mol Sci. 2023-12-7

[5]
Alliance between titans: combination strategies of CAR-T cell therapy and oncolytic virus for the treatment of hematological malignancies.

Ann Hematol. 2024-8

[6]
A first case report of using chimeric antigen receptor T-cell immunotherapy to treat high-risk smoldering multiple myeloma.

J Transl Int Med. 2023-9-2

[7]
Combination of immune checkpoint blockade and targeted gene regulation of angiogenesis for facilitating antitumor immunotherapy.

Front Bioeng Biotechnol. 2023-3-13

[8]
CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies.

Front Immunol. 2023

[9]
Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy.

Drug Deliv Transl Res. 2023-7

[10]
Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?

Cancers (Basel). 2022-12-7

本文引用的文献

[1]
Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial.

Lancet Oncol. 2018-11-12

[2]
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

N Engl J Med. 2016-10-6

[3]
Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma.

N Engl J Med. 2016-8-25

[4]
Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma.

N Engl J Med. 2015-6-2

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索