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实体瘤嵌合抗原受体 T 细胞免疫疗法的障碍和应对策略。

Obstacles and Coping Strategies of CAR-T Cell Immunotherapy in Solid Tumors.

机构信息

Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou, China.

Key Laboratory of the Digestive System Tumors of Gansu Province, Second Hospital of Lanzhou University, Lanzhou, China.

出版信息

Front Immunol. 2021 May 19;12:687822. doi: 10.3389/fimmu.2021.687822. eCollection 2021.


DOI:10.3389/fimmu.2021.687822
PMID:34093592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8170155/
Abstract

Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that enables T cells to express specific CARs on their surface, then returns these T cells to tumor patients to kill the corresponding tumor cells. Significant strides in CAR-T cell immunotherapy against hematologic malignancies have elicited research interest among scholars in the treatment of solid tumors. Nonetheless, in contrast with the efficacy of CAR-T cell immunotherapy in the treatment of hematologic malignancies, its general efficacy against solid tumors is insignificant. This has been attributed to the complex biological characteristics of solid tumors. CAR-T cells play a better role in solid tumors, for instance by addressing obstacles including the lack of specific targets, inhibition of tumor microenvironment (TME), homing barriers of CAR-T cells, differentiation and depletion of CAR-T cells, inhibition of immune checkpoints, trogocytosis of CAR-T cells, tumor antigen heterogeneity, etc. This paper reviews the obstacles influencing the efficacy of CAR-T cell immunotherapy in solid tumors, their mechanism, and coping strategies, as well as economic restriction of CAR-T cell immunotherapy and its solutions. It aims to provide some references for researchers to better overcome the obstacles that affect the efficacy of CAR-T cells in solid tumors.

摘要

嵌合抗原受体 (CAR) T 细胞免疫疗法是近年来迅速发展起来的一种过继免疫疗法。它是一种新型的治疗方法,可以使 T 细胞在其表面表达特定的 CAR,然后将这些 T 细胞回输给肿瘤患者以杀死相应的肿瘤细胞。CAR-T 细胞免疫疗法在血液恶性肿瘤方面的显著进展引起了学者们对实体瘤治疗的研究兴趣。然而,与 CAR-T 细胞免疫疗法在血液恶性肿瘤治疗中的疗效相比,其对实体瘤的总体疗效并不显著。这归因于实体瘤复杂的生物学特性。CAR-T 细胞在实体瘤中发挥更好的作用,例如通过解决缺乏特定靶点、肿瘤微环境 (TME) 抑制、CAR-T 细胞归巢障碍、CAR-T 细胞分化和耗竭、免疫检查点抑制、CAR-T 细胞 trogocytosis、肿瘤抗原异质性等障碍。本文综述了影响 CAR-T 细胞免疫疗法在实体瘤中疗效的障碍及其机制和应对策略,以及 CAR-T 细胞免疫疗法的经济限制及其解决方案。旨在为研究人员提供一些参考,以更好地克服影响 CAR-T 细胞在实体瘤中疗效的障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/ed9f2c78fca6/fimmu-12-687822-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/9e91f7a5fc25/fimmu-12-687822-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/b1c17c321b58/fimmu-12-687822-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/36e4751f22a3/fimmu-12-687822-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/08d7147d64f7/fimmu-12-687822-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/555d7c5ac9b0/fimmu-12-687822-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/0eca9c787f4e/fimmu-12-687822-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/ed9f2c78fca6/fimmu-12-687822-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/9e91f7a5fc25/fimmu-12-687822-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/b1c17c321b58/fimmu-12-687822-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/36e4751f22a3/fimmu-12-687822-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/08d7147d64f7/fimmu-12-687822-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/555d7c5ac9b0/fimmu-12-687822-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/0eca9c787f4e/fimmu-12-687822-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa1/8170155/ed9f2c78fca6/fimmu-12-687822-g006.jpg

相似文献

[1]
Obstacles and Coping Strategies of CAR-T Cell Immunotherapy in Solid Tumors.

Front Immunol. 2021

[2]
Perspectives on Chimeric Antigen Receptor T-Cell Immunotherapy for Solid Tumors.

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[3]
Genetic Modification of Cytokine Signaling to Enhance Efficacy of CAR T Cell Therapy in Solid Tumors.

Front Immunol. 2021

[4]
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[5]
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Front Immunol. 2018-7-31

[6]
CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment.

Front Immunol. 2019-2-5

[7]
CAR T-cell therapy for solid tumours.

Lancet Oncol. 2021-7

[8]
Chimeric antigen receptor T cells in solid tumors: a war against the tumor microenvironment.

Sci China Life Sci. 2019-12-23

[9]
Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors.

Mol Cancer. 2018-1-12

[10]
Future perspectives on engineered T cells for cancer.

Trends Cancer. 2024-8

引用本文的文献

[1]
Preclinical evaluation of antitumor activity and toxicity of TROP2-specific CAR-T cells for treatment of triple-negative breast cancer.

J Immunother Cancer. 2025-9-3

[2]
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Med Oncol. 2025-5-31

[3]
Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma.

Biomark Res. 2025-5-1

[4]
The application of emerging immunotherapy in the treatment of prostate cancer: progress, dilemma and promise.

Front Immunol. 2025-3-12

[5]
Expanding the horizon of CAR T cell therapy: from cancer treatment to autoimmune diseases and beyond.

Front Immunol. 2025-2-19

[6]
The efficacy and applicability of chimeric antigen receptor (CAR) T cell-based regimens for primary bone tumors: A comprehensive review of current evidence.

J Bone Oncol. 2024-9-22

[7]
The Biological Significance of Trogocytosis.

Results Probl Cell Differ. 2024

[8]
IL-21- and CXCL9-engineered GPC3-specific CAR-T cells combined with PD-1 blockade enhance cytotoxic activities against hepatocellular carcinoma.

Clin Exp Med. 2024-8-28

[9]
TALEN-edited allogeneic inducible dual CAR T cells enable effective targeting of solid tumors while mitigating off-tumor toxicity.

Mol Ther. 2024-11-6

[10]
Human NK cells and cancer.

Oncoimmunology. 2024

本文引用的文献

[1]
Precise T cell recognition programs designed by transcriptionally linking multiple receptors.

Science. 2020-11-27

[2]
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Oncolytic Adenovirus Armed with BiTE, Cytokine, and Checkpoint Inhibitor Enables CAR T Cells to Control the Growth of Heterogeneous Tumors.

Mol Ther. 2020-5-6

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Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 Have Superior Expansion and Antitumor Activity against Hepatocellular Carcinoma.

Cancer Immunol Res. 2020-1-17

[10]
Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia.

Blood. 2020-3-5

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