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嵌合抗原受体工程化细胞免疫疗法的当前挑战与新出现的机遇

Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.

作者信息

Liu Yong, Duan Yifei, Du Zefan, Lu Bo, Liu Su, Li Lindi, Tian Mengyao, Li Liang, Yao Ran, Ouyang Cheng, Yang Mo, Chen Chun

机构信息

Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China.

Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China.

出版信息

Exp Hematol Oncol. 2025 Jul 2;14(1):92. doi: 10.1186/s40164-025-00683-y.


DOI:10.1186/s40164-025-00683-y
PMID:40604935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12224691/
Abstract

Chimeric antigen receptor (CAR) engineered cellular immunotherapy offers the potential for precise targeting and elimination of tumor cells, providing a tailored approach to cancer treatment. CAR-T cells demonstrate significant anti-tumor activity among these therapies. Nonetheless, these therapies may trigger adverse effects, including inflammatory and neurotoxic reactions during treatment. Recent efforts have been directed toward enhancing efficacy by optimizing CAR design or modulating its activity. Compared to CAR-T cells, CAR-engineered natural killer cells (CAR-NK) present notable advantages, including various sources and diminished toxicity, and are gaining recognition in clinical research. CAR-macrophages (CAR-M), while sharing antigenic domains similar to those of CAR-T cells, display superior capabilities in antigen presentation and tumor penetration. As a result, there is significant enthusiasm surrounding investigations into CAR-NK and CAR-M cell immunotherapies. This review explores the existing environment and obstacles associated with immunotherapies that utilize CAR-T, CAR-NK, and CAR-M cells to inspire novel pathways for forthcoming clinical applications.

摘要

嵌合抗原受体(CAR)工程化细胞免疫疗法为精准靶向和消除肿瘤细胞提供了可能,为癌症治疗提供了一种量身定制的方法。在这些疗法中,CAR-T细胞表现出显著的抗肿瘤活性。尽管如此,这些疗法可能会引发不良反应,包括治疗期间的炎症和神经毒性反应。最近的努力旨在通过优化CAR设计或调节其活性来提高疗效。与CAR-T细胞相比,CAR工程化自然杀伤细胞(CAR-NK)具有显著优势,包括来源多样和毒性降低,并且在临床研究中越来越受到认可。CAR巨噬细胞(CAR-M)虽然与CAR-T细胞共享相似的抗原结构域,但在抗原呈递和肿瘤渗透方面表现出卓越的能力。因此,围绕CAR-NK和CAR-M细胞免疫疗法的研究引起了极大的关注。本综述探讨了与利用CAR-T、CAR-NK和CAR-M细胞的免疫疗法相关的现有环境和障碍,以激发未来临床应用的新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/f8c6e41fc2bb/40164_2025_683_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/9e556b616bc4/40164_2025_683_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/f6ab5eaf052c/40164_2025_683_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/3a6116bd47d7/40164_2025_683_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/bff1fe0b912f/40164_2025_683_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/f8c6e41fc2bb/40164_2025_683_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/9e556b616bc4/40164_2025_683_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/f6ab5eaf052c/40164_2025_683_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/3a6116bd47d7/40164_2025_683_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/bff1fe0b912f/40164_2025_683_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/12224691/f8c6e41fc2bb/40164_2025_683_Fig5_HTML.jpg

相似文献

[1]
Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.

Exp Hematol Oncol. 2025-7-2

[2]
Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner.

Mol Ther. 2025-1-3

[3]
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

[4]
B cell antigens: A key to optimizing CAR-T cell therapy.

Int Rev Immunol. 2025-6-19

[5]
CAR-NK, a Splendid Strategy for Cancer, Especially for Gynecologic Tumor.

Immun Inflamm Dis. 2025-6

[6]
Mitigation and Management of Common Toxicities Associated with the Administration of CAR-T Therapies in Oncology Patients.

Drug Saf. 2025-3-19

[7]
Single-cell-guided identification of logic-gated antigen combinations for designing effective and safe CAR therapy.

bioRxiv. 2025-3-19

[8]
Breaking barriers: CAR-NK cell therapy breakthroughs in female-related cancers.

Biomed Pharmacother. 2025-6

[9]
Managing allorejection in off-the-shelf CAR-engineered cell therapies.

Mol Ther. 2024-11-26

[10]
Chimeric antigen receptor cell therapy: A revolutionary approach transforming cancer treatment to autoimmune disease therapy.

Autoimmun Rev. 2025-6-23

本文引用的文献

[1]
CAR-macrophage therapy for HER2-overexpressing advanced solid tumors: a phase 1 trial.

Nat Med. 2025-4

[2]
Revolutionizing cancer treatment: the emerging potential and potential challenges of self-processed CAR cell therapy.

Theranostics. 2024-10-28

[3]
The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.

Exp Hematol Oncol. 2024-12-4

[4]
Combining the induced pluripotent stem cell (iPSC) technology with chimeric antigen receptor (CAR)-based immunotherapy: recent advances, challenges, and future prospects.

Front Cell Dev Biol. 2024-11-18

[5]
A New Outcomes-Based Payment Plan From a Chinese Company to Improve Patient Affordability of CAR-T Product.

Int J Health Policy Manag. 2024

[6]
Chimeric antigen receptor-T cell therapy for T cell-derived hematological malignancies.

Exp Hematol Oncol. 2024-11-28

[7]
High-throughput screening for optimizing adoptive T cell therapies.

Exp Hematol Oncol. 2024-11-13

[8]
New insights into CAR T-cell hematological toxicities: manifestations, mechanisms, and effective management strategies.

Exp Hematol Oncol. 2024-11-9

[9]
Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand.

Mol Ther Oncol. 2024-10-5

[10]
Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.

J Hematol Oncol. 2024-11-5

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