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嵌合抗原受体 T 细胞疗法在实体瘤应用中的困境与可能的解决方案。

The dilemmas and possible solutions for CAR-T cell therapy application in solid tumors.

机构信息

Department of Oncology, Air Force Medical Center, PLA, Beijing, China; National Centre for International Research in Cell and Gene Therapy, Sino British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.

National Centre for International Research in Cell and Gene Therapy, Sino British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.

出版信息

Cancer Lett. 2024 Jun 1;591:216871. doi: 10.1016/j.canlet.2024.216871. Epub 2024 Apr 10.


DOI:10.1016/j.canlet.2024.216871
PMID:38604310
Abstract

Chimeric antigen receptor T (CAR-T) cell therapy, as an adoptive immunotherapy, is playing an increasingly important role in the treatment of malignant tumors. CAR-T cells are referred to as "living drugs" as they not only target tumor cells directly, but also induce long-term immune memory that has the potential to provide long-lasting protection. CD19.CAR-T cells have achieved complete response rates of over 90 % for acute lymphoblastic leukemia and over 60 % for non-Hodgkin's lymphoma. However, the response rate of CAR-T cells in the treatment of solid tumors remains extremely low and the side effects potentially severe. In this review, we discuss the limitations that the solid tumor microenvironment poses for CAR-T application and the solutions that are being developed to address these limitations, in the hope that in the near future, CAR-T cell therapy for solid tumors can attain the same success rates as are now being seen clinically for hematological malignancies.

摘要

嵌合抗原受体 T(CAR-T)细胞疗法作为一种过继性免疫疗法,在恶性肿瘤的治疗中发挥着越来越重要的作用。CAR-T 细胞被称为“活的药物”,因为它们不仅直接靶向肿瘤细胞,还诱导具有潜在提供长期保护作用的长期免疫记忆。CD19.CAR-T 细胞在急性淋巴细胞白血病中的完全缓解率超过 90%,在非霍奇金淋巴瘤中的完全缓解率超过 60%。然而,CAR-T 细胞在实体瘤治疗中的反应率仍然极低,且潜在的副作用严重。在这篇综述中,我们讨论了实体瘤微环境对 CAR-T 应用的限制,以及正在开发的解决这些限制的方法,希望在不久的将来,CAR-T 细胞疗法治疗实体瘤能够达到与目前临床上治疗血液恶性肿瘤相同的成功率。

相似文献

[1]
The dilemmas and possible solutions for CAR-T cell therapy application in solid tumors.

Cancer Lett. 2024-6-1

[2]
Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells.

Front Immunol. 2018-7-31

[3]
Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives.

Curr Res Transl Med. 2017-9

[4]
CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?

Mol Ther. 2020-11-4

[5]
Advanced Strategies of CAR-T Cell Therapy in Solid Tumors and Hematological Malignancies.

Recent Pat Anticancer Drug Discov. 2024

[6]
Manipulating the tumor microenvironment by adoptive cell transfer of CAR T-cells.

Mamm Genome. 2018-7-9

[7]
Engineering CAR-T Cells for Next-Generation Cancer Therapy.

Cancer Cell. 2020-10-12

[8]
Clinical investigation of CAR T cells for solid tumors: Lessons learned and future directions.

Pharmacol Ther. 2019-10-16

[9]
[Mechanisms of resistance and escape to CAR-T cells].

Bull Cancer. 2021-10

[10]
Chimeric antigen receptor-engineered T-cell therapy for liver cancer.

Hepatobiliary Pancreat Dis Int. 2018-5-24

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Front Immunol. 2025-8-19

[2]
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[3]
Challenges in the preclinical design and assessment of CAR-T cells.

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[4]
Inhibition of TFF3 improves the infiltration and function of CD8 T cells by downregulating the expression of PD-L1 in colorectal cancer.

Int J Colorectal Dis. 2025-8-5

[5]
Nanobodies and their derivatives: pioneering the future of cancer immunotherapy.

Cell Commun Signal. 2025-6-5

[6]
Revolutionising cancer intervention: the repercussions of CAR-T cell therapy on modern oncology practices.

Med Oncol. 2025-5-31

[7]
Clinical development of immuno-oncology therapeutics.

Cancer Lett. 2025-5-1

[8]
Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors.

Curr Issues Mol Biol. 2025-1-31

[9]
Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform 'cold' tumors into 'hot' tumors.

Mol Cancer. 2024-12-23

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

J Hematol Oncol. 2024-11-5

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