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Characterization of clinical grade CD19 chimeric antigen receptor T cells produced using automated CliniMACS Prodigy system.

作者信息

Zhang Wei, Jordan Kimberly R, Schulte Brian, Purev Enkhtsetseg

机构信息

Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA,

Division of Immunology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

出版信息

Drug Des Devel Ther. 2018 Oct 5;12:3343-3356. doi: 10.2147/DDDT.S175113. eCollection 2018.


DOI:10.2147/DDDT.S175113
PMID:30323566
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6181073/
Abstract

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating acute lymphoblastic leukemia and non-Hodgkin's lymphoma with high rate complete responses. However, the broad clinical application of CAR T-cell therapy has been challenging, largely due to the lack of widespread ability to produce and high cost of CAR T-cell products using traditional methods of production. Automated cell processing in a closed system has emerged as a potential method to increase the feasibility of producing CAR T cells locally at academic centers due to its minimal reliance on experienced labor, thereby making the process less expensive and more consistent than traditional methods of production. METHOD: In this study, we describe the successful production of clinical grade CD19 CAR T cells using the Miltenyi CliniMACS Prodigy Automated Cell Processor at University of Colorado Anschutz Medical Campus in a rapid manner with a high frequent CD19 CAR expression. RESULTS: The final CAR T-cell product is highly active, low in immune suppression, and absent in exhaustion. Full panel cytokine assays also showed elevated production of Th1 cytokines upon IL-2 stimulation when specifically killing CD19+ target cells. CONCLUSION: These results demonstrate the feasibility of producing CAR T cells locally in a university hospital setting using automated cell processor for future clinical applications.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/b541e6659c82/dddt-12-3343Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/9811c05e1162/dddt-12-3343Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/dbf04809ef4b/dddt-12-3343Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/691fa6cecec7/dddt-12-3343Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/b11587ab3fc5/dddt-12-3343Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/0778754104af/dddt-12-3343Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/0d7d121e8fbc/dddt-12-3343Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/b541e6659c82/dddt-12-3343Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/9811c05e1162/dddt-12-3343Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/dbf04809ef4b/dddt-12-3343Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/691fa6cecec7/dddt-12-3343Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/b11587ab3fc5/dddt-12-3343Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/0778754104af/dddt-12-3343Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/0d7d121e8fbc/dddt-12-3343Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/6181073/b541e6659c82/dddt-12-3343Fig7.jpg

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[4]
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[5]
Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand.

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[6]
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[7]
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[8]
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本文引用的文献

[1]
CAR T cell immunotherapy for human cancer.

Science. 2018-3-23

[2]
Closed-system manufacturing of CD19 and dual-targeted CD20/19 chimeric antigen receptor T cells using the CliniMACS Prodigy device at an academic medical center.

Cytotherapy. 2017-12-26

[3]
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.

N Engl J Med. 2017-12-28

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TIM-3 Engagement Promotes Effector Memory T Cell Differentiation of Human Antigen-Specific CD8 T Cells by Activating mTORC1.

J Immunol. 2017-12-15

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Leuk Lymphoma. 2018-7

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Hum Gene Ther. 2017-10

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Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes.

J Clin Invest. 2017-9-1

[9]
Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts.

EMBO Mol Med. 2017-9

[10]
Global Manufacturing of CAR T Cell Therapy.

Mol Ther Methods Clin Dev. 2016-12-31

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