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CAR T 细胞的临床生产:一种有前途的治疗方法的基础。

Clinical manufacturing of CAR T cells: foundation of a promising therapy.

机构信息

Cell Therapy and Cell Engineering Facility, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

出版信息

Mol Ther Oncolytics. 2016 Jun 15;3:16015. doi: 10.1038/mto.2016.15. eCollection 2016.


DOI:10.1038/mto.2016.15
PMID:27347557
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4909095/
Abstract

The treatment of cancer patients with autologous T cells expressing a chimeric antigen receptor (CAR) is one of the most promising adoptive cellular therapy approaches. Reproducible manufacturing of high-quality, clinical-grade CAR-T cell products is a prerequisite for the wide application of this technology. Product quality needs to be built-in within every step of the manufacturing process. We summarize herein the requirements and logistics to be considered, as well as the state of the art manufacturing platforms available. CAR-T cell therapy may be on the verge of becoming standard of care for a few clinical indications. Yet, many challenges pertaining to manufacturing standardization and product characterization remain to be overcome in order to achieve broad usage and eventual commercialization of this therapeutic modality.

摘要

用嵌合抗原受体 (CAR) 修饰的自体 T 细胞治疗癌症患者是最有前途的过继性细胞治疗方法之一。可重复性地生产高质量、临床级别的 CAR-T 细胞产品是该技术广泛应用的前提。产品质量需要内置在制造过程的每一个步骤中。我们在此总结了需要考虑的要求和物流,以及现有的先进制造平台。CAR-T 细胞疗法可能即将成为少数临床适应症的标准治疗方法。然而,为了实现这种治疗方式的广泛应用和最终商业化,仍有许多与制造标准化和产品特性相关的挑战需要克服。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c41/4909095/ebec1a48861d/mto201615-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c41/4909095/ebec1a48861d/mto201615-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c41/4909095/ebec1a48861d/mto201615-f1.jpg

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本文引用的文献

[1]
Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease.

J Clin Oncol. 2016-4-1

[2]
Chimeric antigen receptor T cell therapy: 25years in the making.

Blood Rev. 2016-5

[3]
Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates.

Transfusion. 2016-2

[4]
Automated Cell Enrichment of Cytomegalovirus-specific T cells for Clinical Applications using the Cytokine-capture System.

J Vis Exp. 2015-10-5

[5]
Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo.

Leukemia. 2016-2

[6]
Concise Review: Process Development Considerations for Cell Therapy.

Stem Cells Transl Med. 2015-10

[7]
Multiplex Genome-Edited T-cell Manufacturing Platform for "Off-the-Shelf" Adoptive T-cell Immunotherapies.

Cancer Res. 2015-7-16

[8]
Optimizing the production of suspension cells using the G-Rex "M" series.

Mol Ther Methods Clin Dev. 2014-5-14

[9]
IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors .

Oncoimmunology. 2015-1-23

[10]
Fully automated expansion and activation of clinical-grade natural killer cells for adoptive immunotherapy.

Cytotherapy. 2015-5

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