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靶向多发性骨髓瘤中的B细胞成熟抗原:设计、挑战及未来方向。

Targeting BCMA in multiple myeloma: designs, challenges, and future directions.

作者信息

Hu Yi, Xie Yuetao, Wang Xiaodong, Yang Lufeng, Geng He, Yi Zugang, Zhang Yao, Ma Lin, Chen Fang

机构信息

Department of Anesthesiology, Shenzhen Children's Hospital, Shenzhen, 518038, Guangdong, China.

Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, 518038, Guangdong, China.

出版信息

Cancer Immunol Immunother. 2025 Feb 1;74(3):77. doi: 10.1007/s00262-024-03913-0.


DOI:10.1007/s00262-024-03913-0
PMID:39891674
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11787132/
Abstract

Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking immunotherapy, demonstrating significant efficacy in treating B cell malignancies. In the context of multiple myeloma (MM), B cell maturation antigen (BCMA) has been identified as a critical target, driving the development of CAR T cell therapies designed to address this plasma cell cancer. Various CAR designs, utilizing different BCMA recognition domains, have yielded promising clinical results, leading to the approval of two BCMA-targeting CAR T cell therapies by the US Food and Drug Administration (FDA) for the treatment of MM. This review uniquely examines the BCMA CAR T cell landscape, emphasizing the design of recognition domains, clinical efficacy, and patient outcomes. It critically addresses emerging challenges such as antigen escape and toxicity profiles, which have surfaced alongside therapeutic advances. Moreover, the review spotlights cutting-edge developments, including dual-targeting CAR T strategies, advancements in CAR T cell manufacturing, and innovative allogeneic CAR T approaches utilizing healthy donor cells. By detailing both the breakthroughs and ongoing challenges in BCMA CAR T cell therapy, this review offers a comprehensive perspective on the current state and future possibilities of CAR T cell therapy for MM and its expanding role in treating hematologic malignancies and beyond.

摘要

嵌合抗原受体(CAR)T细胞疗法已成为一种开创性的免疫疗法,在治疗B细胞恶性肿瘤方面显示出显著疗效。在多发性骨髓瘤(MM)的背景下,B细胞成熟抗原(BCMA)已被确定为一个关键靶点,推动了旨在治疗这种浆细胞癌的CAR T细胞疗法的发展。各种利用不同BCMA识别域的CAR设计已经产生了有前景的临床结果,导致美国食品药品监督管理局(FDA)批准了两种靶向BCMA的CAR T细胞疗法用于治疗MM。本综述独特地审视了BCMA CAR T细胞领域,强调了识别域的设计、临床疗效和患者预后。它批判性地探讨了诸如抗原逃逸和毒性特征等新出现的挑战,这些挑战随着治疗进展而出现。此外,该综述突出了前沿进展,包括双靶点CAR T策略、CAR T细胞制造的进步以及利用健康供体细胞的创新同种异体CAR T方法。通过详细阐述BCMA CAR T细胞疗法中的突破和持续挑战,本综述全面地呈现了CAR T细胞疗法治疗MM的现状和未来可能性,以及其在治疗血液系统恶性肿瘤及其他疾病中不断扩大的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8e/11787132/03380a537fbc/262_2024_3913_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8e/11787132/ab848aec0f8b/262_2024_3913_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8e/11787132/03380a537fbc/262_2024_3913_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8e/11787132/ab848aec0f8b/262_2024_3913_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d8e/11787132/03380a537fbc/262_2024_3913_Fig2_HTML.jpg

相似文献

[1]
Targeting BCMA in multiple myeloma: designs, challenges, and future directions.

Cancer Immunol Immunother. 2025-2-1

[2]
BCMA-targeted therapies in multiple myeloma: advances, challenges and future prospects.

Med Oncol. 2025-5-8

[3]
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

[4]
[CAR-T cells immunotherapy in multiple myeloma: Present and future].

Bull Cancer. 2021-10

[5]
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Mol Ther. 2019-4-8

[6]
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

[7]
B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma.

Clin Cancer Res. 2013-1-23

[8]
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

[9]
Chimeric antigen receptor T cell targeting B cell maturation antigen immunotherapy is promising for multiple myeloma.

Ann Hematol. 2019-1-28

[10]
Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy.

Front Immunol. 2024

引用本文的文献

[1]
Targets for CAR Therapy in Multiple Myeloma.

Int J Mol Sci. 2025-6-24

[2]
Achieving stringent complete remission in relapsed/refractory multiple myeloma with liver extramedullary disease after CAR‑T cell therapy: A case report.

Oncol Lett. 2025-3-28

本文引用的文献

[1]
Anti-BCMA/GPRC5D bispecific CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, single-centre, phase 1 trial.

Lancet Haematol. 2024-10

[2]
Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA Adverse Events Reporting System.

Blood. 2024-5-16

[3]
T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy.

Nat Med. 2024-4

[4]
Rapid anti-myeloma activity by T cells expressing an anti-BCMA CAR with a human heavy-chain-only antigen-binding domain.

Mol Ther. 2024-2-7

[5]
Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma.

Nat Med. 2023-9

[6]
Fibrin-associated large B-cell lymphoma shows frequent mutations related to immune surveillance and PTEN.

Blood. 2023-9-14

[7]
γ-Secretase inhibitor in combination with BCMA chimeric antigen receptor T-cell immunotherapy for individuals with relapsed or refractory multiple myeloma: a phase 1, first-in-human trial.

Lancet Oncol. 2023-7

[8]
Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy.

J Immunother Cancer. 2023-6

[9]
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.

N Engl J Med. 2023-7-27

[10]
Identification of potential resistance mechanisms and therapeutic targets for the relapse of BCMA CAR-T therapy in relapsed/refractory multiple myeloma through single-cell sequencing.

Exp Hematol Oncol. 2023-5-8

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