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用细胞因子为嵌合抗原受体T细胞提供能量。

Fueling chimeric antigen receptor T cells with cytokines.

作者信息

Jin Jin, Cheng Jiali, Huang Meijuan, Luo Hui, Zhou Jianfeng

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.

Immunotherapy Research Center for Hematologic Diseases of Hubei Province Wuhan, Hubei, China.

出版信息

Am J Cancer Res. 2020 Dec 1;10(12):4038-4055. eCollection 2020.


DOI:
PMID:33414984
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7783740/
Abstract

Chimeric antigen receptor (CAR)-T therapy started a new era of tumor treatment, especially for hematological malignancies. However, many challenges remain, including low-level proliferation and short-term persistence, insufficient CAR T-cell trafficking, suppressive tumor microenvironment (TME), frequent adverse events and the unaffordable manufacturing process. Cytokines are pleiotropic hormones involved in multiple processes of immunity, including activation, expansion, differentiation, and migration of immune cells. Both pre-clinical models and clinical trials showed that armoring CAR-T cells with cytokines strengthened the anti-tumor responses of CAR T cells. This review looked into the key role of cytokines as a promoter of anti-tumor activities of CAR-T cells and consequently a facilitator of clinical translation, mainly, from cytokines of the common γ-chains family, chemokines and chemokine receptors, immunosuppressive molecules and pro-inflammatory cytokines.

摘要

嵌合抗原受体(CAR)-T细胞疗法开启了肿瘤治疗的新时代,尤其是对于血液系统恶性肿瘤。然而,仍然存在许多挑战,包括低水平增殖和短期持久性、CAR T细胞归巢不足、抑制性肿瘤微环境(TME)、频繁的不良事件以及难以承受的生产过程。细胞因子是多效性激素,参与免疫的多个过程,包括免疫细胞的激活、扩增、分化和迁移。临床前模型和临床试验均表明,用细胞因子武装CAR-T细胞可增强CAR T细胞的抗肿瘤反应。本综述探讨了细胞因子作为CAR-T细胞抗肿瘤活性促进剂以及临床转化促进剂的关键作用,主要涉及常见γ链家族的细胞因子、趋化因子和趋化因子受体、免疫抑制分子和促炎细胞因子。

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Fueling chimeric antigen receptor T cells with cytokines.

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引用本文的文献

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[2]
Depletion of Tregs from CD4 CAR-T cells enhances the tumoricidal effect of CD8 CAR-T cells in anti-CD19 CAR-T therapy.

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[4]
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[5]
Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma.

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[6]
CAR T Cell Therapy in Hematological Malignancies: Implications of the Tumor Microenvironment and Biomarkers on Efficacy and Toxicity.

Int J Mol Sci. 2022-6-22

[7]
CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies.

Cells. 2022-5-31

[8]
Chimeric Antigen Receptor (CAR) T Cell Therapy for Glioblastoma.

Cancer Treat Res. 2022

[9]
Chimeric antigen receptor engineered T cells and their application in the immunotherapy of solid tumours.

Expert Rev Mol Med. 2022-1-28

[10]
Genetic Modification of Cytokine Signaling to Enhance Efficacy of CAR T Cell Therapy in Solid Tumors.

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本文引用的文献

[1]
Coexpression of IL7 and CCL21 Increases Efficacy of CAR-T Cells in Solid Tumors without Requiring Preconditioned Lymphodepletion.

Clin Cancer Res. 2020-10-15

[2]
Design and Characterization of an "All-in-One" Lentiviral Vector System Combining Constitutive Anti-G CAR Expression and Inducible Cytokines.

Cancers (Basel). 2020-2-6

[3]
Interleukin-23 engineering improves CAR T cell function in solid tumors.

Nat Biotechnol. 2020-2-3

[4]
TGF-β inhibition via CRISPR promotes the long-term efficacy of CAR T cells against solid tumors.

JCI Insight. 2020-2-27

[5]
Engineered IL-7 Receptor Enhances the Therapeutic Effect of AXL-CAR-T Cells on Triple-Negative Breast Cancer.

Biomed Res Int. 2020-1-2

[6]
CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma.

Eur J Immunol. 2020-2-10

[7]
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

[8]
IL-18R-dependent and independent pathways account for IL-18-enhanced antitumor ability of CAR-T cells.

FASEB J. 2019-12-6

[9]
Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies.

Front Oncol. 2019-11-21

[10]
CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors.

Nat Commun. 2019-9-5

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