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血液肿瘤学中除CD19和BCMA之外的新型嵌合抗原受体T细胞(CAR-T)疗法的未来展望

Future perspectives on novel CAR-T therapeutics beyond CD19 and BCMA in onco-hematology.

作者信息

Ershova Alina, Goldaeva Alexandra, Staliarova Alena, Bulatov Emil, Petukhov Alexey, Barlev Nikolai

机构信息

Laboratory of Molecular Oncology, National Laboratory Astana, Astana, Kazakhstan.

Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, Kazakhstan.

出版信息

Front Immunol. 2025 Jul 14;16:1592377. doi: 10.3389/fimmu.2025.1592377. eCollection 2025.


DOI:10.3389/fimmu.2025.1592377
PMID:40726984
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12301417/
Abstract

CAR-T cell therapy is a type of adoptive immune therapy that relies on the specific targeting of cytotoxic T-cells to eliminate the malfunctioning cells in the body. Genetic engineering allows the generation of an almost infinite variety of chimeric antigen receptors (CAR) to ensure specificity for antigens on the surface of target cells. Therefore, CAR-T appears to be a powerful and versatile therapy for the treatment of various diseases, including cancer. Recently, CAR-T has emerged as a significant advancement in the management of hematological tumors, particularly B-cell malignancies, mainly due to the presence of specific antigens such as CD19 and BCMA. As a result, the market for CAR-T therapy is experiencing significant growth. However, the problem of relapses remains and warrants the search for new therapeutic approaches, including CAR-T technology. In this case, one of the major challenges is finding and evaluating new targets for CAR-T in terms of their likelihood of success. Here we propose a set of established criteria for the evaluation of potential targets for CAR-T cell therapy to treat hematological malignancies. These criteria include assessing the target in terms of its biological characteristics, such as expression level, cellular localization, tissue specificity, and clinical aspects, including unmet clinical needs and the success of clinical trials. Using these criteria, we validate our prediction of the next CAR-T cell therapy targets that will likely emerge soon.

摘要

嵌合抗原受体(CAR)T细胞疗法是一种过继性免疫疗法,它依靠细胞毒性T细胞的特异性靶向作用来清除体内功能失常的细胞。基因工程使得人们能够生成几乎无限多样的嵌合抗原受体,以确保对靶细胞表面抗原的特异性。因此,CAR-T似乎是一种治疗包括癌症在内的各种疾病的强大且通用的疗法。最近,CAR-T已成为血液肿瘤尤其是B细胞恶性肿瘤治疗方面的一项重大进展,这主要归因于CD19和BCMA等特定抗原的存在。结果,CAR-T疗法市场正在经历显著增长。然而,复发问题依然存在,这就需要寻找包括CAR-T技术在内的新治疗方法。在这种情况下,主要挑战之一是从成功可能性的角度寻找和评估CAR-T的新靶点。在此,我们提出一套既定标准,用于评估CAR-T细胞疗法治疗血液恶性肿瘤的潜在靶点。这些标准包括从生物学特性(如表达水平、细胞定位、组织特异性)以及临床方面(如未满足的临床需求和临床试验的成功情况)来评估靶点。利用这些标准,我们验证了对可能很快出现的下一批CAR-T细胞疗法靶点的预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eae/12301417/406e44bb18a0/fimmu-16-1592377-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eae/12301417/53dcf31acebe/fimmu-16-1592377-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eae/12301417/7a26ef7ab76a/fimmu-16-1592377-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eae/12301417/406e44bb18a0/fimmu-16-1592377-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eae/12301417/53dcf31acebe/fimmu-16-1592377-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eae/12301417/7a26ef7ab76a/fimmu-16-1592377-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eae/12301417/406e44bb18a0/fimmu-16-1592377-g003.jpg

相似文献

[1]
Future perspectives on novel CAR-T therapeutics beyond CD19 and BCMA in onco-hematology.

Front Immunol. 2025-7-14

[2]
A new sort of cells for chimeric antigen receptor T-cell therapies-isolating CD14CD127 T cells for chimeric antigen receptor T-cell manufacture.

Cytotherapy. 2025-4-18

[3]
Obecabtagene autoleucel, a novel CD19-directed CAR T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: the future for reducing toxicity and T-cell exhaustion?

Expert Rev Hematol. 2025-6-23

[4]
CAR-T Cells Therapy in Glioblastoma: A Systematic Review on Molecular Targets and Treatment Strategies.

Int J Mol Sci. 2024-6-29

[5]
Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma.

Cochrane Database Syst Rev. 2021-9-13

[6]
Current Anti-Myeloma Chimeric Antigen Receptor-T Cells: Novel Targets and Methods.

Balkan Med J. 2025-7-1

[7]
ARI0003: Co-transduced CD19/BCMA dual-targeting CAR-T cells for the treatment of non-Hodgkin lymphoma.

Mol Ther. 2025-1-8

[8]
From spheroids to organoids: next-generation models for CAR-T cell therapy research in solid tumors.

Front Immunol. 2025-7-11

[9]
From concept to cure: The evolution of CAR-T cell therapy.

Mol Ther. 2025-5-7

[10]
Research progress of targeted BCMA CAR-T therapy for relapsed/refractory multiple myeloma antigen-negative relapse.

Best Pract Res Clin Haematol. 2025-6

本文引用的文献

[1]
Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.

Blood Cancer J. 2024-8-7

[2]
Talicabtagene Autoleucel: First Approval.

Mol Diagn Ther. 2024-7

[3]
Harnessing CD3 diversity to optimize CAR T cells.

Nat Immunol. 2023-12

[4]
Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma.

Leukemia. 2024-1

[5]
Equecabtagene Autoleucel: First Approval.

Mol Diagn Ther. 2023-11

[6]
Selinexor: Targeting a novel pathway in multiple myeloma.

EJHaem. 2023-5-15

[7]
Relapsed Acute Lymphoblastic Leukemia.

Indian J Pediatr. 2024-2

[8]
Immunotherapies targeting GPRC5D in relapsed or refractory multiple myeloma: latest updates from 2022 ASH Annual Meeting.

J Hematol Oncol. 2023-6-5

[9]
CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies.

Front Immunol. 2023

[10]
GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial.

Lancet Haematol. 2023-2

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