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儿科脑肿瘤的免疫治疗新时代:嵌合抗原受体 T 细胞疗法。

New Era of Immunotherapy in Pediatric Brain Tumors: Chimeric Antigen Receptor T-Cell Therapy.

机构信息

School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.

Division of Pediatric Neurosurgery, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112201, Taiwan.

出版信息

Int J Mol Sci. 2021 Feb 27;22(5):2404. doi: 10.3390/ijms22052404.


DOI:10.3390/ijms22052404
PMID:33673696
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7957810/
Abstract

Immunotherapy, including chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, cancer vaccines, and dendritic cell therapy, has been incorporated as a fifth modality of modern cancer care, along with surgery, radiation, chemotherapy, and target therapy. Among them, CAR T-cell therapy emerges as one of the most promising treatments. In 2017, the first two CAR T-cell drugs, tisagenlecleucel and axicabtagene ciloleucel for B-cell acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), respectively, were approved by the Food and Drug Administration (FDA). In addition to the successful applications to hematological malignancies, CAR T-cell therapy has been investigated to potentially treat solid tumors, including pediatric brain tumor, which serves as the leading cause of cancer-associated death for children and adolescents. However, the employment of CAR T-cell therapy in pediatric brain tumors still faces multiple challenges, such as CAR T-cell transportation and expansion through the blood-brain barrier, and identification of the specific target antigen on the tumor surface and immunosuppressive tumor microenvironment. Nevertheless, encouraging outcomes in both clinical and preclinical trials are coming to light. In this article, we outline the current propitious progress and discuss the obstacles needed to be overcome in order to unveil a new era of treatment in pediatric brain tumors.

摘要

免疫疗法,包括嵌合抗原受体(CAR)T 细胞疗法、免疫检查点抑制剂、癌症疫苗和树突状细胞疗法,已被纳入现代癌症治疗的第五种模式,与手术、放疗、化疗和靶向治疗并列。其中,CAR T 细胞疗法是最有前途的治疗方法之一。2017 年,FDA 批准了两种 CAR T 细胞药物,tisagenlecleucel 和 axicabtagene ciloleucel,分别用于治疗 B 细胞急性淋巴细胞白血病(ALL)和弥漫性大 B 细胞淋巴瘤(DLBCL)。除了成功应用于血液恶性肿瘤外,CAR T 细胞疗法还被用于治疗实体肿瘤,包括小儿脑肿瘤,它是儿童和青少年癌症相关死亡的主要原因。然而,CAR T 细胞疗法在小儿脑肿瘤中的应用仍面临多个挑战,如 CAR T 细胞通过血脑屏障的运输和扩增,以及肿瘤表面特定靶抗原和免疫抑制性肿瘤微环境的识别。尽管如此,临床和临床前试验中的令人鼓舞的结果正在显现。本文概述了目前有利的进展,并讨论了为揭开小儿脑肿瘤治疗新时代需要克服的障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5395/7957810/36a8ae06f885/ijms-22-02404-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5395/7957810/4726c7554f0b/ijms-22-02404-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5395/7957810/d1264150f002/ijms-22-02404-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5395/7957810/36a8ae06f885/ijms-22-02404-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5395/7957810/4726c7554f0b/ijms-22-02404-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5395/7957810/d1264150f002/ijms-22-02404-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5395/7957810/36a8ae06f885/ijms-22-02404-g003.jpg

相似文献

[1]
New Era of Immunotherapy in Pediatric Brain Tumors: Chimeric Antigen Receptor T-Cell Therapy.

Int J Mol Sci. 2021-2-27

[2]
Emerging trends in gene-modified-based chimeric antigen receptor-engineered T-cellular therapy for malignant tumors: The lesson from leukemia to pediatric brain tumors.

J Chin Med Assoc. 2020-8

[3]
Current Progress in CAR-T Cell Therapy for Solid Tumors.

Int J Biol Sci. 2019-9-7

[4]
CAR T-cells to treat brain tumors.

Brain Res Bull. 2023-5

[5]
CAR-T cells for pediatric brain tumors: Present and future.

Bull Cancer. 2021-10

[6]
Current progress in chimeric antigen receptor T cell therapy for glioblastoma multiforme.

Cancer Med. 2021-8

[7]
Chimeric Antigen Receptor-Engineered T-Cells - A New Way and Era for Lymphoma Treatment.

Recent Pat Anticancer Drug Discov. 2019

[8]
Chimeric antigen receptor-engineered T-cell therapy for liver cancer.

Hepatobiliary Pancreat Dis Int. 2018-5-24

[9]
The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice.

Front Immunol. 2020

[10]
Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.

Immunol Res. 2021-12

引用本文的文献

[1]
CAR-T cells for pediatric malignancies: Past, present, future and nursing implications.

Asia Pac J Oncol Nurs. 2023-8-3

[2]
Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment.

Cancers (Basel). 2021-12-28

本文引用的文献

[1]
Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR T-cell delivery.

Neuro Oncol. 2021-6-1

[2]
Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies.

Int J Mol Sci. 2020-11-17

[3]
Chimeric antigen receptor T-cell therapy in glioblastoma: charging the T cells to fight.

J Transl Med. 2020-11-11

[4]
CAR T Cell Therapy for Pediatric Brain Tumors.

Front Oncol. 2020-8-12

[5]
How I treat adverse effects of CAR-T cell therapy.

ESMO Open. 2020-8

[6]
Emerging trends in gene-modified-based chimeric antigen receptor-engineered T-cellular therapy for malignant tumors: The lesson from leukemia to pediatric brain tumors.

J Chin Med Assoc. 2020-8

[7]
Disialoganglioside GD2 Expression in Solid Tumors and Role as a Target for Cancer Therapy.

Front Oncol. 2020-7-7

[8]
CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape.

Front Immunol. 2020

[9]
Surmounting the obstacles that impede effective CAR T cell trafficking to solid tumors.

J Leukoc Biol. 2020-10

[10]
Modern Radiotherapy for Pediatric Brain Tumors.

Cancers (Basel). 2020-6-11

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