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多发性骨髓瘤中CAR疗法的靶点

Targets for CAR Therapy in Multiple Myeloma.

作者信息

Bezborodova Olga A, Trunova Galina V, Nemtsova Elena R, Khokhlova Varvara A, Venediktova Julia B, Morozova Natalia B, Vorontsova Maria S, Plyutinskaya Anna D, Zharova Elena P, Shegai Peter V, Kaprin Andrey D

机构信息

Moscow Hertsen Research Institute of Oncology-Branch of the National Medical Radiology Research Center, Ministry of Health of the Russian Federation, Moscow 125284, Russia.

出版信息

Int J Mol Sci. 2025 Jun 24;26(13):6051. doi: 10.3390/ijms26136051.


DOI:10.3390/ijms26136051
PMID:40649828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12249785/
Abstract

Multiple myeloma (MM or plasma cell myeloma) is a heterogenous B-cell malignant tumor that typically exhibits a high recurrence rate, resistance to drugs, and molecular diversity of tumor subclones. Given the limited efficacy of standard therapy options, cellular immunotherapy featuring a chimeric antigen receptor (CAR) has proven tangible potential in treatment for relapsed and refractory forms of MM. The rational choice of a tumor target which shows high selectivity, stable expression, and biological significance is key to the successful implementation of CAR therapy. This review has summarized and analyzed data from the literature on biological properties, the features of expression, and the clinical development stages of CAR cell products for MM treatment which target BCMA, GPRC5D, FcRH5, SLAMF7, CD38, CD138, TACI, APRIL, CD19, TNFR2, CD44v6, CD70, NKG2D ligands, etc. Special focus is on strategic approaches to overcoming antigenic escape, such as multi-specific CAR constructs, logical activation sequences, and controlled safety systems. The analysis underscores the need for integrating the molecular selection of targets with cutting-edge bioengineering solutions as a key trend for raising the efficacy, stability, and safety of cellular therapy in the case of MM.

摘要

多发性骨髓瘤(MM或浆细胞骨髓瘤)是一种异质性B细胞恶性肿瘤,通常具有高复发率、耐药性以及肿瘤亚克隆的分子多样性。鉴于标准治疗方案的疗效有限,以嵌合抗原受体(CAR)为特征的细胞免疫疗法已在复发和难治性MM的治疗中显示出切实的潜力。合理选择具有高选择性、稳定表达和生物学意义的肿瘤靶点是成功实施CAR治疗的关键。本综述总结并分析了文献中有关用于MM治疗的靶向BCMA、GPRC5D、FcRH5、SLAMF7、CD38、CD138、TACI、APRIL、CD19、TNFR2、CD44v6、CD70、NKG2D配体等的CAR细胞产品的生物学特性、表达特征及临床开发阶段的数据。特别关注克服抗原逃逸的策略方法,如多特异性CAR构建体、逻辑激活序列和可控安全系统。分析强调,将靶点的分子选择与前沿生物工程解决方案相结合是提高MM细胞治疗疗效、稳定性和安全性的关键趋势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ea2/12249785/7049d54643e7/ijms-26-06051-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ea2/12249785/7049d54643e7/ijms-26-06051-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ea2/12249785/7049d54643e7/ijms-26-06051-g001.jpg

相似文献

[1]
Targets for CAR Therapy in Multiple Myeloma.

Int J Mol Sci. 2025-6-24

[2]
Current Anti-Myeloma Chimeric Antigen Receptor-T Cells: Novel Targets and Methods.

Balkan Med J. 2025-7-1

[3]
Case Report: Summary of multiple CAR-T expansions in anti-BCMA/GPRC5D bispecific CAR-T cell therapy for multiple myeloma.

Front Immunol. 2025-6-6

[4]
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.

Int J Mol Sci. 2024-5-3

[5]
Bispecific Antibodies as Bridging to BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma.

Blood Cancer Discov. 2025-1-8

[6]
Myeloma cell-intrinsic ANXA1 elevation and T cell dysfunction contribute to BCMA-negative relapse after CAR-T therapy.

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[7]
CAR-T Cells Therapy in Glioblastoma: A Systematic Review on Molecular Targets and Treatment Strategies.

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[8]
Genetic and epigenetic mechanisms of GPRC5D loss after anti-GPRC5D CAR T-cell therapy in multiple myeloma.

Blood. 2025-7-10

[9]
TIGIT blockade in the context of BCMA-CART cell therapy does not augment efficacy in a multiple myeloma mouse model.

Oncoimmunology. 2025-12

[10]
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Cochrane Database Syst Rev. 2021-9-13

本文引用的文献

[1]
Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies.

Cancers (Basel). 2025-4-26

[2]
Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells.

Blood. 2025-5-13

[3]
Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.

Int J Biol Sci. 2025-3-24

[4]
From molecular design to clinical translation: dual-targeted CAR-T strategies in cancer immunotherapy.

Int J Biol Sci. 2025-3-31

[5]
Strategies to overcome tumour relapse caused by antigen escape after CAR T therapy.

Mol Cancer. 2025-4-28

[6]
CAR-NK cell therapy: promise and challenges in solid tumors.

Front Immunol. 2025-4-7

[7]
Anti-GPRC5D CAR T-cell therapy as a salvage treatment in patients with progressive multiple myeloma after anti-BCMA CAR T-cell therapy: a single-centre, single-arm, phase 2 trial.

Lancet Haematol. 2025-5

[8]
Expanding the CAR toolbox with high throughput screening strategies for CAR domain exploration: a comprehensive review.

J Immunother Cancer. 2025-4-9

[9]
Cost-Effectiveness of Elranatamab Versus Current Therapies for the Management of Patients with Triple-Class Exposed, Relapsed and Refractory Multiple Myeloma, Including Other Bispecific and Physician's Choice of Treatment in Spain.

Oncol Ther. 2025-4-7

[10]
The clinical landscape of CAR NK cells.

Exp Hematol Oncol. 2025-3-27

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