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

B 细胞成熟抗原是多发性骨髓瘤过继性 T 细胞治疗的一个有前途的靶点。

B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma.

机构信息

Experimental Transplantation and Immunology Branch; Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.

出版信息

Clin Cancer Res. 2013 Apr 15;19(8):2048-60. doi: 10.1158/1078-0432.CCR-12-2422. Epub 2013 Jan 23.


DOI:10.1158/1078-0432.CCR-12-2422
PMID:23344265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3630268/
Abstract

PURPOSE: Multiple myeloma is a usually incurable malignancy of plasma cells. New therapies are urgently needed for multiple myeloma. Adoptive transfer of chimeric antigen receptor (CAR)-expressing T cells is a promising new therapy for hematologic malignancies, but an ideal target antigen for CAR-expressing T-cell therapies for multiple myeloma has not been identified. B-cell maturation antigen (BCMA) is a protein that has been reported to be selectively expressed by B-lineage cells including multiple myeloma cells. Our goal was to determine if BCMA is a suitable target for CAR-expressing T cells. EXPERIMENTAL DESIGN: We conducted an assessment of BCMA expression in normal human tissues and multiple myeloma cells by flow cytometry, quantitative PCR, and immunohistochemistry. We designed and tested novel anti-BCMA CARs. RESULTS: BCMA had a restricted RNA expression pattern. Except for expression in plasma cells, BCMA protein was not detected in normal human tissues. BCMA was not detected on primary human CD34(+) hematopoietic cells. We detected uniform BCMA cell-surface expression on primary multiple myeloma cells from five of five patients. We designed the first anti-BCMA CARs to be reported and we transduced T cells with lentiviral vectors encoding these CARs. The CARs gave T cells the ability to specifically recognize BCMA. The anti-BCMA-CAR-transduced T cells exhibited BCMA-specific functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication. Importantly, anti-BCMA-CAR-transduced T cells recognized and killed primary multiple myeloma cells. CONCLUSIONS: BCMA is a suitable target for CAR-expressing T cells, and adoptive transfer of anti-BCMA-CAR-expressing T cells is a promising new strategy for treating multiple myeloma.

摘要

目的:多发性骨髓瘤是一种通常无法治愈的浆细胞恶性肿瘤。多发性骨髓瘤迫切需要新的治疗方法。嵌合抗原受体(CAR)表达 T 细胞的过继转移是血液恶性肿瘤的一种很有前途的新疗法,但尚未确定用于多发性骨髓瘤 CAR 表达 T 细胞治疗的理想靶抗原。B 细胞成熟抗原(BCMA)是一种已被报道在包括多发性骨髓瘤细胞在内的 B 细胞谱系细胞中选择性表达的蛋白。我们的目标是确定 BCMA 是否是 CAR 表达 T 细胞的合适靶标。

实验设计:我们通过流式细胞术、定量 PCR 和免疫组织化学评估了正常人类组织和多发性骨髓瘤细胞中的 BCMA 表达。我们设计并测试了新型抗 BCMA CAR。

结果:BCMA 的 RNA 表达模式受到限制。除了在浆细胞中表达外,BCMA 蛋白在正常人类组织中未检测到。BCMA 未在原代人类 CD34+造血细胞上检测到。我们在来自五名患者的原代多发性骨髓瘤细胞上检测到均匀的 BCMA 细胞表面表达。我们设计了第一批据报道的抗 BCMA CAR,并通过慢病毒载体转导 T 细胞以编码这些 CAR。这些 CAR 赋予 T 细胞特异性识别 BCMA 的能力。抗 BCMA-CAR 转导的 T 细胞表现出 BCMA 特异性功能,包括细胞因子产生、增殖、细胞毒性和体内肿瘤清除。重要的是,抗 BCMA-CAR 转导的 T 细胞识别并杀死原代多发性骨髓瘤细胞。

结论:BCMA 是 CAR 表达 T 细胞的合适靶标,过继转移抗 BCMA-CAR 表达 T 细胞是治疗多发性骨髓瘤的一种很有前途的新策略。

相似文献

[1]
B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma.

Clin Cancer Res. 2013-1-23

[2]
Effective Targeting of Multiple B-Cell Maturation Antigen-Expressing Hematological Malignances by Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor T Cells.

Hum Gene Ther. 2018-5

[3]
A transgene-encoded truncated human epidermal growth factor receptor for depletion of anti- B-cell maturation antigen CAR-T cells.

Cell Immunol. 2021-5

[4]
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Mol Ther. 2019-4-8

[5]
T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma.

J Clin Oncol. 2018-5-29

[6]
Treatment of Multiple Myeloma Using Chimeric Antigen Receptor T Cells with Dual Specificity.

Cancer Immunol Res. 2020-12

[7]
GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells.

Sci Transl Med. 2019-3-27

[8]
Optimized BCMA/CS1 bispecific TRuC-T cells secreting IL-7 and CCL21 robustly control multiple myeloma.

Front Immunol. 2024-12-24

[9]
Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy.

Front Immunol. 2018-8-10

[10]
Therapeutic potential of third-generation chimeric antigen receptor T cells targeting B cell maturation antigen for treating multiple myeloma.

Clin Exp Med. 2024-4-29

引用本文的文献

[1]
Resistance Mechanisms to BCMA Targeting Bispecific Antibodies and CAR T-Cell Therapies in Multiple Myeloma.

Cells. 2025-7-15

[2]
FcRL1, a New B-Cell-Activating Co-Receptor.

Int J Mol Sci. 2025-6-30

[3]
Current Anti-Myeloma Chimeric Antigen Receptor-T Cells: Novel Targets and Methods.

Balkan Med J. 2025-7-1

[4]
Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma.

Nat Commun. 2025-7-4

[5]
The progression of multiple myeloma is regulated by LILRB1 via the GATA2-SAGE1 pathway.

Br J Haematol. 2025-7

[6]
Quantification of total sBCMA in human plasma by peptide-level immunocapture LC-MS/MS.

J Mass Spectrom Adv Clin Lab. 2025-4-17

[7]
Belantamab Mafodotin Monotherapy for Multiply-Relapsed Myeloma: A Retrospective Study From the United Kingdom and the Republic of Ireland.

EJHaem. 2025-4-30

[8]
Long-term follow-up of BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma.

J Immunother Cancer. 2025-3-28

[9]
From gene modules to gene markers: an integrated AI-human approach selects CD38 to represent plasma cell-associated transcriptional signatures.

Front Med (Lausanne). 2025-3-12

[10]
Understanding the Toxicity Profile of Approved ADCs.

Pharmaceutics. 2025-2-14

本文引用的文献

[1]
Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival.

Br J Haematol. 2012-7-18

[2]
B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells.

Blood. 2011-12-8

[3]
Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor.

Mol Ther. 2011-11-29

[4]
Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma.

Leukemia. 2011-8-19

[5]
Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias.

Blood. 2011-8-17

[6]
Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia.

N Engl J Med. 2011-8-10

[7]
Monoclonal antibodies in the treatment of multiple myeloma.

Br J Haematol. 2011-9

[8]
Reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma: a concise review.

Clin Lymphoma Myeloma Leuk. 2011-4-20

[9]
CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients.

J Clin Invest. 2011-4-11

[10]
Treatment of multiple myeloma.

Nat Rev Clin Oncol. 2011-4-26

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