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用于多发性骨髓瘤治疗的基于非传统同种异体抗BCMA嵌合抗原受体的免疫细胞疗法。

Non-Conventional Allogeneic Anti-BCMA Chimeric Antigen Receptor-Based Immune Cell Therapies for Multiple Myeloma Treatment.

作者信息

Du Zhicheng, Zhu Sumin, Zhang Xi, Gong Zhiyuan, Wang Shu

机构信息

Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.

出版信息

Cancers (Basel). 2023 Jan 17;15(3):567. doi: 10.3390/cancers15030567.


DOI:10.3390/cancers15030567
PMID:36765526
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9913487/
Abstract

MM, characterized by the progressive accumulation of clonal plasma cells in bone marrow, remains a severe medical problem globally. Currently, almost all MM patients who have received standard treatments will eventually relapse. Autologous anti-BCMA CAR-T cells are one of the FDA-approved immunotherapy cell-based products for treating adults with relapsed or refractory (r/r) multiple myeloma. However, this type of CAR-T cell product has several limitations, including high costs, long manufacturing times, and possible manufacturing failure, which significantly hinder its wider application for more patients. In this review, we summarized the current development stage of applying other types of immune cells to bring the anti-BCMA CAR-T therapy from autologous to allogeneic. In general, anti-BCMA CAR gene-edited αβ T cells and CAR-Natural Killer (NK) cells are at the forefront, with multiple clinical trials ongoing, while CAR-γδ T cells and CAR-invariant Natural Killer T (iNKT) cells are still in pre-clinical studies. Other immune cells such as macrophages, B cells, and dendritic cells have been mainly developed to target other antigens and have the potential to be used to target BCMA. Nevertheless, additional regulatory requirements might need to be taken into account in developing these non-conventional allogenic anti-BCMA CAR-based cell products.

摘要

多发性骨髓瘤(MM)的特征是骨髓中克隆性浆细胞进行性积聚,在全球范围内仍然是一个严重的医学问题。目前,几乎所有接受标准治疗的MM患者最终都会复发。自体抗BCMA嵌合抗原受体T细胞(CAR-T)是美国食品药品监督管理局(FDA)批准的用于治疗复发或难治性(r/r)成年多发性骨髓瘤的基于免疫疗法的细胞产品之一。然而,这类CAR-T细胞产品存在一些局限性,包括成本高、生产时间长以及可能出现生产失败等问题,这严重阻碍了其在更多患者中的广泛应用。在这篇综述中,我们总结了应用其他类型免疫细胞将抗BCMA CAR-T疗法从自体转变为异体的当前发展阶段。总体而言,抗BCMA CAR基因编辑的αβ T细胞和CAR-自然杀伤(NK)细胞处于前沿,多项临床试验正在进行中,而CAR-γδ T细胞和CAR-不变自然杀伤T(iNKT)细胞仍处于临床前研究阶段。其他免疫细胞,如巨噬细胞、B细胞和树突状细胞,主要是针对其他抗原进行开发,并且有可能用于靶向BCMA。尽管如此,在开发这些基于非传统异体抗BCMA CAR的细胞产品时,可能需要考虑额外的监管要求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e729/9913487/99d2fa15de40/cancers-15-00567-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e729/9913487/ed04f0ed8fcb/cancers-15-00567-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e729/9913487/16a75326c1c9/cancers-15-00567-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e729/9913487/99d2fa15de40/cancers-15-00567-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e729/9913487/ed04f0ed8fcb/cancers-15-00567-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e729/9913487/16a75326c1c9/cancers-15-00567-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e729/9913487/99d2fa15de40/cancers-15-00567-g003.jpg

相似文献

[1]
Non-Conventional Allogeneic Anti-BCMA Chimeric Antigen Receptor-Based Immune Cell Therapies for Multiple Myeloma Treatment.

Cancers (Basel). 2023-1-17

[2]
Anti-myeloma efficacy of CAR-iNKT is enhanced with a long-acting IL-7, rhIL-7-hyFc.

Blood Adv. 2023-10-24

[3]
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Mol Ther. 2019-4-8

[4]
Overview of anti-BCMA CAR-T immunotherapy for multiple myeloma and relapsed/refractory multiple myeloma.

Scand J Immunol. 2020-6-17

[5]
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

[6]
Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Single Center Analysis of Two Clinical Trials.

Front Immunol. 2021

[7]
Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma.

Front Immunol. 2022

[8]
Triple MAPK inhibition salvaged a relapsed post-BCMA CAR-T cell therapy multiple myeloma patient with a BRAF V600E subclonal mutation.

J Hematol Oncol. 2022-8-17

[9]
Beyond BCMA: the next wave of CAR T cell therapy in multiple myeloma.

Front Oncol. 2024-5-10

[10]
sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma.

Curr Issues Mol Biol. 2022-3-24

引用本文的文献

[1]
HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma.

Front Immunol. 2025-4-4

[2]
Allogeneic chimeric antigen receptors (CARs) as an "off-the-shelf" therapy in multiple myeloma.

Immunotherapy. 2025-2

[3]
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

[4]
Contribution of long-lived plasma cells to antibody-mediated allograft rejection.

Clin Transplant Res. 2024-12-31

[5]
Are we there yet? CAR-T therapy in multiple myeloma.

Br J Haematol. 2024-12

[6]
Updates on CAR T cell therapy in multiple myeloma.

Biomark Res. 2024-9-12

[7]
Recent updates on allogeneic CAR-T cells in hematological malignancies.

Cancer Cell Int. 2024-9-3

[8]
Translating B cell immunology to the treatment of antibody-mediated allograft rejection.

Nat Rev Nephrol. 2024-4

[9]
T Cell Based Immunotherapy for Cancer: Approaches and Strategies.

Vaccines (Basel). 2023-4-13

本文引用的文献

[1]
Cas-CLOVER is a novel high-fidelity nuclease for safe and robust generation of T-enriched allogeneic CAR-T cells.

Mol Ther Nucleic Acids. 2022-6-29

[2]
Vγ9Vδ2 T cells expressing a BCMA-Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth.

PLoS One. 2022

[3]
Innovative Strategies to Improve the Clinical Application of NK Cell-Based Immunotherapy.

Front Immunol. 2022

[4]
Consensus Statement: Importance of Timely Access to Multiple Myeloma Diagnosis and Treatment in Central America and the Caribbean.

J Hematol. 2022-2

[5]
FDA approves second BCMA-targeted CAR-T cell therapy.

Nat Rev Drug Discov. 2022-4

[6]
Cancer statistics in China and United States, 2022: profiles, trends, and determinants.

Chin Med J (Engl). 2022-2-9

[7]
Harnessing natural killer cells for the treatment of multiple myeloma.

Semin Oncol. 2022-2

[8]
Off-the-shelf Vδ1 gamma delta T cells engineered with glypican-3 (GPC-3)-specific chimeric antigen receptor (CAR) and soluble IL-15 display robust antitumor efficacy against hepatocellular carcinoma.

J Immunother Cancer. 2021-12

[9]
piggyBac system to co-express NKG2D CAR and IL-15 to augment the persistence and anti-AML activity of human peripheral blood NK cells.

Mol Ther Methods Clin Dev. 2021-11-4

[10]
BCMA in Multiple Myeloma-A Promising Key to Therapy.

J Clin Med. 2021-9-10

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