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嵌合抗原受体 (CAR) T 细胞疗法治疗多发性骨髓瘤。

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

机构信息

Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC, USA.

Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC, USA.

出版信息

Pharmacol Ther. 2022 Apr;232:108007. doi: 10.1016/j.pharmthera.2021.108007. Epub 2021 Sep 25.


DOI:10.1016/j.pharmthera.2021.108007
PMID:34582835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8930424/
Abstract

Although treatment outcomes of multiple myeloma patients have improved significantly during the last two decades, myeloma is still an incurable disease. There are newly emerging immunotherapies to treat multiple myeloma including monoclonal antibodies, antibody-drug conjugate, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy. Impressive response rate and clinical efficacy in heavily pretreated myeloma patients led to the FDA approval of the first myeloma CAR-T therapy in March 2021. Among many different targets for myeloma CAR-T therapies, B Cell Maturation Antigen (BCMA) has been the most successful target so far, but other targets which can be used either for single-target or dual-target CAR-T's are actively being explored. Clinical efficacy and safety of current myeloma CAR-T therapies will be presented here. Potential mechanisms leading to resistance include clearance of CAR-T cells, antigenic escape, and immunosuppressive tumor microenvironment. Novel strategies to enhance myeloma CAR-T will also be described. In this article, we provide a comprehensive review of the current data and the future directions of myeloma CAR-T therapies.

摘要

虽然多发性骨髓瘤患者的治疗结果在过去二十年中显著改善,但骨髓瘤仍然是一种不可治愈的疾病。目前有新出现的免疫疗法来治疗多发性骨髓瘤,包括单克隆抗体、抗体药物偶联物、双特异性抗体和嵌合抗原受体 (CAR) T 细胞疗法。在经过大量预处理的骨髓瘤患者中,令人印象深刻的缓解率和临床疗效导致 FDA 在 2021 年 3 月批准了首个骨髓瘤 CAR-T 疗法。在骨髓瘤 CAR-T 疗法的众多不同靶点中,B 细胞成熟抗原 (BCMA) 是迄今为止最成功的靶点,但其他可用于单靶点或双靶点 CAR-T 的靶点也在积极探索中。本文将介绍目前骨髓瘤 CAR-T 疗法的临床疗效和安全性。导致耐药的潜在机制包括 CAR-T 细胞清除、抗原逃逸和免疫抑制肿瘤微环境。还将描述增强骨髓瘤 CAR-T 的新策略。本文全面综述了骨髓瘤 CAR-T 疗法的现有数据和未来方向。

相似文献

[1]
Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma.

Pharmacol Ther. 2022-4

[2]
Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy.

Front Immunol. 2018-8-10

[3]
Chimeric antigen receptor T-cell therapy for multiple myeloma.

Front Immunol. 2022

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

Bull Cancer. 2021-10

[5]
Chimeric Antigen Receptor T Cell Therapy for Myeloma: Where Are We Now and What Is Needed to Move Chimeric Antigen Receptor T Cells Forward to Earlier Lines of Therapy? Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.

Transplant Cell Ther. 2024-1

[6]
BCMA CAR-T cells in multiple myeloma-ready for take-off?

Leuk Lymphoma. 2024-2

[7]
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Expert Opin Biol Ther. 2019-7-11

[8]
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Cancer Lett. 2023-1-28

[9]
Clinical experience of CAR T cells for multiple myeloma.

Best Pract Res Clin Haematol. 2021-9

[10]
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J Oncol Pharm Pract. 2022-6

引用本文的文献

[1]
Global, regional, and national burden of multiple myeloma from 1990 to 2021 and projections for 2040: a systematic analysis for the global burden of disease 2021 study.

Front Epidemiol. 2025-4-29

[2]
β-Arrestin 2 as a Prognostic Indicator and Immunomodulatory Factor in Multiple Myeloma.

Cells. 2025-3-26

[3]
Strategies for salvage therapy post CAR-T therapy failure in refractory/relapsed multiple myeloma patients.

Front Pharmacol. 2025-3-17

[4]
Advancing Multiple Myeloma Immunotherapy: A Review of Chimeric Antigen Receptor T-Cell and Bispecific T-Cell Engagers Cell Therapies in Revolutionizing Treatment.

Iran J Med Sci. 2025-1-1

[5]
Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy.

Front Immunol. 2024

[6]
Role of Immune Cells and Immunotherapy in Multiple Myeloma.

Life (Basel). 2024-4-1

[7]
Progress and prospect of ASCT combined with CAR-T therapy in the treatment of multiple myeloma.

Ther Adv Hematol. 2024-3-13

[8]
In Vitro Functionality and Endurance of GMP-Compliant Point-of-Care BCMA.CAR-T Cells at Different Timepoints of Cryopreservation.

Int J Mol Sci. 2024-1-23

[9]
Oncolytic vaccinia virus and cancer immunotherapy.

Front Immunol. 2023

[10]
Advanced Strategies of CAR-T Cell Therapy in Solid Tumors and Hematological Malignancies.

Recent Pat Anticancer Drug Discov. 2024

本文引用的文献

[1]
CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma.

Gene Ther. 2021-9

[2]
Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.

N Engl J Med. 2021-2-25

[3]
Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma.

Nat Med. 2021-4

[4]
Sequential CD19 and BCMA-specific CAR T-cell treatment elicits sustained remission of relapsed and/or refractory myeloma.

Cancer Med. 2021-1

[5]
Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma.

J Hematol Oncol. 2020-12-3

[6]
Defining an Optimal Dual-Targeted CAR T-cell Therapy Approach Simultaneously Targeting BCMA and GPRC5D to Prevent BCMA Escape-Driven Relapse in Multiple Myeloma.

Blood Cancer Discov. 2020-9

[7]
Treatment of Multiple Myeloma Using Chimeric Antigen Receptor T Cells with Dual Specificity.

Cancer Immunol Res. 2020-12

[8]
BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma.

J Immunother. 2020

[9]
Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma.

Haematologica. 2021-4-1

[10]
A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma.

Blood. 2020-4-9

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