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嵌合抗原受体T细胞(CAR-T细胞):血液癌症的早期成功与实体瘤面临的挑战

CAR-T cells: Early successes in blood cancer and challenges in solid tumors.

作者信息

Dana Hassan, Chalbatani Ghanbar Mahmoodi, Jalali Seyed Amir, Mirzaei Hamid Reza, Grupp Stephan A, Suarez Eloah Rabello, Rapôso Catarina, Webster Thomas J

机构信息

Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 13145-158, Iran.

Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran.

出版信息

Acta Pharm Sin B. 2021 May;11(5):1129-1147. doi: 10.1016/j.apsb.2020.10.020. Epub 2020 Nov 2.


DOI:10.1016/j.apsb.2020.10.020
PMID:34094824
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8144892/
Abstract

New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. For hematologic malignancies, adoptive and engineered cell therapies are being widely developed, using cells such as T lymphocytes, as well as natural killer (NK) cells, dendritic cells, and potentially others. Among these adoptive cell therapies, the most active and advanced therapy involves chimeric antigen receptor (CAR)-T cells, which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition, activation and killing of cancers, such as leukemia and lymphoma. Two autologous CAR-T products have been approved by several health authorities, starting with the U.S. Food and Drug Administration (FDA) in 2017. These products have shown powerful, inducing, long-lasting effects against B cell cancers in many cases. In distinction to the results seen in hematologic malignancies, the field of using CAR-T products against solid tumors is in its infancy. Targeting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges. The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies, allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors successfully.

摘要

癌症免疫疗法已开发出了新方法,显示出利用免疫系统治疗和消除癌症的能力。对于许多实体瘤而言,检查点抑制剂疗法已展现出前景。对于血液系统恶性肿瘤,过继性和工程化细胞疗法正在广泛开展,所使用的细胞包括T淋巴细胞、自然杀伤(NK)细胞、树突状细胞以及其他可能的细胞。在这些过继性细胞疗法中,最活跃且最先进的疗法涉及嵌合抗原受体(CAR)-T细胞,即通过嵌合抗原受体来重新定向特异性,从而使T细胞能够识别、激活并杀伤白血病和淋巴瘤等癌症的T细胞。自2017年美国食品药品监督管理局(FDA)率先批准以来,已有两种自体CAR-T产品获多个卫生部门批准。在许多情况下,这些产品已显示出对B细胞癌症具有强大、诱导性且持久的疗效。与血液系统恶性肿瘤的治疗结果不同,使用CAR-T产品治疗实体瘤的领域尚处于起步阶段。靶向实体瘤并将CAR-T细胞输送到免疫抑制微环境中都是重大挑战。本综述的目的是总结CAR-T细胞设计和制造的一些最新进展,这些进展已在血液系统恶性肿瘤治疗中取得成功,使读者了解要将CAR-T疗法成功扩展至实体瘤必须克服的障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d548/8144892/ca9da0712250/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d548/8144892/41683caf019e/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d548/8144892/f93ec1b684a6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d548/8144892/ca9da0712250/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d548/8144892/41683caf019e/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d548/8144892/f93ec1b684a6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d548/8144892/ca9da0712250/gr2.jpg

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CAR-T cells: Early successes in blood cancer and challenges in solid tumors.

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[4]
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[2]
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[3]
The role of exosomes in bladder cancer immunotherapy.

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[4]
The Persistent Power of the Taxane/Platin Chemotherapy.

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[6]
Influence of gut microbial metabolites on tumor immunotherapy: mechanisms and potential natural products.

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[7]
Tumor-Associated Extracellular Matrix Obstacles for CAR-T Cell Therapy: Approaches to Overcoming.

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[8]
CAR-engineered T cell therapy as an emerging strategy for treating autoimmune diseases.

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[9]
CAR-macrophage: Breaking new ground in cellular immunotherapy.

Front Cell Dev Biol. 2024-10-3

[10]
The Comparative Oncology of Canine Malignant Melanoma in Targeted Therapy: A Systematic Review of Experiments and Animal Model Reports.

Int J Mol Sci. 2024-9-26

本文引用的文献

[1]
T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road.

Cells. 2020-6-30

[2]
T cell-engaging therapies - BiTEs and beyond.

Nat Rev Clin Oncol. 2020-4-2

[3]
Less is more: reducing the number of administered chimeric antigen receptor T cells in a mouse model using a mathematically guided approach.

Cancer Immunol Immunother. 2020-3-4

[4]
γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity.

Cancer Immunol Res. 2020-2-4

[5]
Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1.

Nat Immunol. 2020-1-20

[6]
Finding the Keys to the CAR: Identifying Novel Target Antigens for T Cell Redirection Immunotherapies.

Int J Mol Sci. 2020-1-14

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Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer.

J Clin Med. 2020-1-9

[8]
CAR T Cells Beyond Cancer: Hope for Immunomodulatory Therapy of Infectious Diseases.

Front Immunol. 2019-11-21

[9]
Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies.

Front Immunol. 2019-11-12

[10]
Multi-antigen-targeted chimeric antigen receptor T cells for cancer therapy.

J Hematol Oncol. 2019-11-29

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