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释放嵌合抗原受体巨噬细胞(CAR-M)疗法在实体瘤中的潜力:一项全面综述。

Unleashing the power of CAR-M therapy in solid tumors: a comprehensive review.

作者信息

Morva Ahsen, Arroyo Ana Belén, Andreeva Liudmila, Tapia-Abellán Ana, Luengo-Gil Ginés

机构信息

Biotechnology Research Group, Climat & Life Sciences, TUBITAK Marmara Research Center, Kocaeli, Türkiye.

Transplant Immunology Research Center of Excellence TIREX, Koc University School of Medicine, Istanbul, Türkiye.

出版信息

Front Immunol. 2025 Jun 12;16:1615760. doi: 10.3389/fimmu.2025.1615760. eCollection 2025.


DOI:10.3389/fimmu.2025.1615760
PMID:40574837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12198237/
Abstract

Chimeric antigen receptor (CAR) macrophage therapy represents a promising new frontier in cancer immunotherapy, with the potential to overcome the limitations of CAR-T cell approaches, particularly in solid tumours. This comprehensive review focuses on the current state and future prospects of CAR macrophage technology, emphasising its applications in solid malignancies across preclinical and early clinical development. The key topics covered included CAR design optimisation, macrophage sources and engineering strategies, mechanisms of antitumour activity, efficacy in animal models, initial clinical trial results, and challenges for broader implementation. The unique properties of macrophages, including tumour penetration and microenvironment modulation, offer significant advantages over T cell-based therapies in solid-tumour settings. However, strategies to enhance persistence, maintain proinflammatory phenotypes, and improve manufacturing are required. Although early research suggests additional applications beyond oncology, including for infectious and inflammatory diseases, this review primarily concentrates on the oncologic potential of CAR-M therapies. Continued optimisation and larger randomised trials will be critical to establish clinical efficacy and define the role of this approach in the treatment of solid tumours.

摘要

嵌合抗原受体(CAR)巨噬细胞疗法是癌症免疫疗法中一个充满希望的新领域,有潜力克服CAR-T细胞疗法的局限性,尤其是在实体瘤治疗方面。这篇全面综述聚焦于CAR巨噬细胞技术的现状与未来前景,着重阐述其在临床前和早期临床开发阶段在实体恶性肿瘤中的应用。涵盖的关键主题包括CAR设计优化、巨噬细胞来源与工程策略、抗肿瘤活性机制、在动物模型中的疗效、初步临床试验结果以及更广泛应用面临的挑战。巨噬细胞的独特特性,包括肿瘤穿透和微环境调节,在实体瘤环境中相对于基于T细胞的疗法具有显著优势。然而,需要采取策略来增强持久性、维持促炎表型并改进生产工艺。尽管早期研究表明CAR-M疗法在肿瘤学之外还有其他应用,包括用于感染性和炎症性疾病,但本综述主要关注其在肿瘤治疗方面的潜力。持续优化和更大规模的随机试验对于确立临床疗效以及明确该方法在实体瘤治疗中的作用至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/88a082cb6de1/fimmu-16-1615760-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/cf2b711d9f08/fimmu-16-1615760-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/a4c4a6a35905/fimmu-16-1615760-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/41b3939ce71e/fimmu-16-1615760-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/7c0259cd5d07/fimmu-16-1615760-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/88a082cb6de1/fimmu-16-1615760-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/cf2b711d9f08/fimmu-16-1615760-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/a4c4a6a35905/fimmu-16-1615760-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/41b3939ce71e/fimmu-16-1615760-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/7c0259cd5d07/fimmu-16-1615760-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/12198237/88a082cb6de1/fimmu-16-1615760-g005.jpg

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引用本文的文献

[1]
Perineural invasion and the "cold" tumor microenvironment in pancreatic cancer: mechanisms of crosstalk and therapeutic opportunities.

Front Immunol. 2025-8-20

本文引用的文献

[1]
CAR macrophages with built-In CD47 blocker combat tumor antigen heterogeneity and activate T cells via cross-presentation.

Nat Commun. 2025-4-30

[2]
Adoptive immune cell therapy for colorectal cancer.

Front Immunol. 2025-4-1

[3]
CAR-T therapy in solid tumors.

Cancer Cell. 2025-4-14

[4]
CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.

Nat Rev Gastroenterol Hepatol. 2025-4-14

[5]
Chimeric antigen receptor therapies: Development, design, and implementation.

J Allergy Clin Immunol. 2025-7

[6]
Reprogram to heal: Macrophage phenotypes as living therapeutics.

Life Sci. 2025-6-15

[7]
CAR T cells in lung cancer: Targeting tumor-associated antigens to revolutionize immunotherapy.

Pathol Res Pract. 2025-5

[8]
The clinical landscape of CAR NK cells.

Exp Hematol Oncol. 2025-3-27

[9]
CAR-T therapy dilemma and innovative design strategies for next generation.

Cell Death Dis. 2025-3-27

[10]
A comprehensive review on targeting diverse immune cells for anticancer therapy: Beyond immune checkpoint inhibitors.

Crit Rev Oncol Hematol. 2025-6

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