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现成的异体嵌合抗原受体 T 细胞:开发与挑战。

'Off-the-shelf' allogeneic CAR T cells: development and challenges.

机构信息

Centre Léon Bérard and Centre de Recherche en Cancérologie de Lyon, Lyon, France.

Cellectis, Paris, France.

出版信息

Nat Rev Drug Discov. 2020 Mar;19(3):185-199. doi: 10.1038/s41573-019-0051-2. Epub 2020 Jan 3.


DOI:10.1038/s41573-019-0051-2
PMID:31900462
Abstract

Autologous chimeric antigen receptor (CAR) T cells have changed the therapeutic landscape in haematological malignancies. Nevertheless, the use of allogeneic CAR T cells from donors has many potential advantages over autologous approaches, such as the immediate availability of cryopreserved batches for patient treatment, possible standardization of the CAR-T cell product, time for multiple cell modifications, redosing or combination of CAR T cells directed against different targets, and decreased cost using an industrialized process. However, allogeneic CAR T cells may cause life-threatening graft-versus-host disease and may be rapidly eliminated by the host immune system. The development of next-generation allogeneic CAR T cells to address these issues is an active area of research. In this Review, we analyse the different sources of T cells for optimal allogeneic CAR-T cell therapy and describe the different technological approaches, mainly based on gene editing, to produce allogeneic CAR T cells with limited potential for graft-versus-host disease. These improved allogeneic CAR-T cell products will pave the way for further breakthroughs in the treatment of cancer.

摘要

自体嵌合抗原受体 (CAR) T 细胞改变了血液系统恶性肿瘤的治疗格局。然而,与自体方法相比,同种异体 CAR T 细胞来自供体具有许多潜在优势,例如可立即获得用于患者治疗的冷冻保存批次,CAR-T 细胞产品可能标准化,有时间进行多次细胞修饰、再给药或针对不同靶点的 CAR T 细胞联合治疗,并且采用工业化流程可降低成本。然而,同种异体 CAR T 细胞可能会导致危及生命的移植物抗宿主病,并且可能会被宿主免疫系统迅速清除。开发解决这些问题的下一代同种异体 CAR T 细胞是一个活跃的研究领域。在这篇综述中,我们分析了用于优化同种异体 CAR-T 细胞治疗的不同 T 细胞来源,并描述了不同的技术方法,主要基于基因编辑,以产生具有有限移植物抗宿主病潜力的同种异体 CAR T 细胞。这些改进的同种异体 CAR-T 细胞产品将为癌症治疗的进一步突破铺平道路。

相似文献

[1]
'Off-the-shelf' allogeneic CAR T cells: development and challenges.

Nat Rev Drug Discov. 2020-1-3

[2]
[Development of allogeneic CAR T-cells].

Bull Cancer. 2021-10

[3]
Allogeneic "Off-the-Shelf" CAR T cells: Challenges and advances.

Best Pract Res Clin Haematol. 2024-9

[4]
Use of Cell and Genome Modification Technologies to Generate Improved "Off-the-Shelf" CAR T and CAR NK Cells.

Front Immunol. 2020

[5]
Potential alternatives to αβ-T cells to prevent graft-versus-host disease (GvHD) in allogeneic chimeric antigen receptor (CAR)-based cancer immunotherapy: A comprehensive review.

Pathol Res Pract. 2024-10

[6]
[Advances in Allogeneic Chimeric Antigen Receptor T Cells].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2023-12-30

[7]
Allogeneic chimeric antigen receptor-modified cells for adoptive cell therapy of cancer.

Expert Opin Biol Ther. 2014-3-24

[8]
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Mol Ther. 2019-4-8

[9]
Challenges and opportunities of allogeneic donor-derived CAR T cells.

Curr Opin Hematol. 2015-11

[10]
Allogeneic CAR-T cells for cancer immunotherapy.

Immunotherapy. 2024

引用本文的文献

[1]
Recent advances in universal chimeric antigen receptor T cell therapy.

J Hematol Oncol. 2025-8-29

[2]
CAR T-cell therapy in autoimmune diseases: a promising frontier on the horizon.

Front Immunol. 2025-8-12

[3]
Unconventional Immunotherapies in Cancer: Opportunities and Challenges.

Pharmaceuticals (Basel). 2025-8-4

[4]
CD44v6 CAR-T Cells Target DNMT3A-Mutant AML: Synergistic Enhancement by Decitabine.

Curr Med Sci. 2025-8-25

[5]
CRISPR/Cas-Based Ex Vivo Gene Therapy and Lysosomal Storage Disorders: A Perspective Beyond Cas9.

Cells. 2025-7-25

[6]
Pharmacovigilance in Cell and Gene Therapy: Evolving Challenges in Risk Management and Long-Term Follow-Up.

Drug Saf. 2025-8-9

[7]
CD7 CAR-T therapy: current developments, improvements, and dilemmas.

Blood Sci. 2025-8-5

[8]
Emerging CAR immunotherapies: broadening therapeutic horizons beyond cancer.

Clin Exp Med. 2025-8-4

[9]
Knowledge-map and bibliometric analysis of scientific research on FDA-approved Chimeric Antigen Receptor T cell products (2015-2024).

Discov Oncol. 2025-8-3

[10]
Research progress on chimeric antigen receptor-based immunotherapy against autoimmune diseases.

Hum Vaccin Immunother. 2025-12

本文引用的文献

[1]
Clinical lessons learned from the first leg of the CAR T cell journey.

Nat Med. 2019-9-9

[2]
Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Multiply Relapsed or Refractory Adult Large B-Cell Lymphoma.

J Clin Oncol. 2019-6-3

[3]
CD19 CAR T cell product and disease attributes predict leukemia remission durability.

J Clin Invest. 2019-3-12

[4]
CRISPR-Cpf1-mediated genome editing and gene regulation in human cells.

Biotechnol Adv. 2018-11-3

[5]
CRISPR/Cas system: A game changing genome editing technology, to treat human genetic diseases.

Gene. 2018-10-26

[6]
Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.

Cancer Cell. 2018-10-8

[7]
Stem cell fate in cancer growth, progression and therapy resistance.

Nat Rev Cancer. 2018-11

[8]
Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo.

Nat Biotechnol. 2018-8-13

[9]
Induction of Chromosomal Translocations with CRISPR-Cas9 and Other Nucleases: Understanding the Repair Mechanisms That Give Rise to Translocations.

Adv Exp Med Biol. 2018

[10]
Driving cars to the clinic for solid tumors.

Gene Ther. 2018-6-7

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