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德国嵌合抗原受体 T(CAR-T)和嵌合抗原受体自然杀伤(CAR-NK)细胞疗法临床试验的现状和展望。

Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany.

机构信息

Children's Hospital, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Goethe-University Frankfurt, Frankfurt am Main, Germany.

Experimental Immunology, Goethe University Frankfurt, Frankfurt am Main, Germany.

出版信息

Gene Ther. 2021 Sep;28(9):513-527. doi: 10.1038/s41434-021-00246-w. Epub 2021 Mar 22.


DOI:10.1038/s41434-021-00246-w
PMID:33753909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8455322/
Abstract

Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. Lately, CAR-NK cell therapies have also come into focus as novel therapeutic options to address hurdles related to CAR-T cell therapies, such as therapy-induced side effects. Currently, more than 500 CAR-T and 17 CAR-NK cell trials are being conducted worldwide including the four CAR-T cell products Kymriah, Yescarta, Tecartus and Breyanzi, which are already available on the market. Most CAR-T cell-based gene therapy products that are under clinical evaluation consist of autologous enriched T cells, whereas CAR-NK cell-based approaches can be generated from allogeneic donors. Besides modification based on a second-generation CAR, more advanced CAR-immune cell therapeutics are being tested, which utilize precise insertion of genes to circumvent graft-versus-host disease (GvHD) or employ a dual targeting approach and adapter CARs in order to avoid therapy resistance caused by antigen loss. In this review, we are going to take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany.

摘要

嵌合抗原受体 (CAR)-T 细胞疗法即将成为治疗血液系统疾病的强大免疫治疗工具,以应对迫切的医疗需求。最近,CAR-NK 细胞疗法也成为解决 CAR-T 细胞疗法相关障碍的新治疗选择,例如治疗相关的副作用。目前,全球正在进行超过 500 项 CAR-T 和 17 项 CAR-NK 细胞试验,包括已经上市的四种 CAR-T 细胞产品 Kymriah、Yescarta、 Tecartus 和 Breyanzi。大多数正在临床评估的基于 CAR-T 细胞的基因治疗产品由自体富集的 T 细胞组成,而基于 CAR-NK 细胞的方法可以由同种异体供体产生。除了基于第二代 CAR 的修饰外,还正在测试更先进的 CAR-免疫细胞疗法,这些疗法利用基因的精确插入来规避移植物抗宿主病 (GvHD),或采用双重靶向方法和适配器 CAR,以避免因抗原丢失引起的治疗耐药性。在这篇综述中,我们将更详细地了解商业 CAR-T 细胞疗法,以及正在德国进行临床试验评估的 CAR-T 和 CAR-NK 细胞产品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ce4/8455322/2b4e8bb11ba8/41434_2021_246_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ce4/8455322/2b4e8bb11ba8/41434_2021_246_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ce4/8455322/2b4e8bb11ba8/41434_2021_246_Fig1_HTML.jpg

相似文献

[1]
Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany.

Gene Ther. 2021-9

[2]
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[3]
Clinical evidence of immunogenicity of CAR-T cell therapies and its implication in the clinical development of CAR-T drug products.

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[4]
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[5]
CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity.

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[6]
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[7]
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[8]
Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.

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[9]
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[10]
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本文引用的文献

[1]
Adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cells: an off-the-shelf cellular therapeutic for universal tumor targeting.

Oncoimmunology. 2020-9-29

[2]
Immunotherapy with NK cells: recent developments in gene modification open up new avenues.

Oncoimmunology. 2020-9-2

[3]
Highly Efficient Generation of Transgenically Augmented CAR NK Cells Overexpressing CXCR4.

Front Immunol. 2020

[4]
The Great War of Today: Modifications of CAR-T Cells to Effectively Combat Malignancies.

Cancers (Basel). 2020-7-24

[5]
CAR T cells: Living HIV drugs.

Rev Med Virol. 2020-11

[6]
EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma.

Oncologist. 2020-10

[7]
KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma.

N Engl J Med. 2020-4-2

[8]
High Cytotoxic Efficiency of Lentivirally and Alpharetrovirally Engineered CD19-Specific Chimeric Antigen Receptor Natural Killer Cells Against Acute Lymphoblastic Leukemia.

Front Immunol. 2020-1-24

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The European Medicines Agency Review of Kymriah (Tisagenlecleucel) for the Treatment of Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma.

Oncologist. 2020-2

[10]
Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors.

N Engl J Med. 2020-2-6

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