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Translational Implications for Off-the-shelf Immune Cells Expressing Chimeric Antigen Receptors.

作者信息

Torikai Hiroki, Cooper Laurence Jn

机构信息

Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Ziopharm Oncology Inc., Boston, Massachusetts, USA.

出版信息

Mol Ther. 2016 Aug;24(7):1178-86. doi: 10.1038/mt.2016.106. Epub 2016 May 16.


DOI:10.1038/mt.2016.106
PMID:27203439
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5088751/
Abstract

Chimeric antigen receptor (CAR) endows specificity to T-cells independent of human leukocyte antigen (HLA). This enables one immunoreceptor to directly target the same surface antigen on different subsets of tumor cells from multiple HLA-disparate recipients. Most approaches manufacture individualized CAR(+)T-cells from the recipient or HLA-compatible donor, which are revealing promising clinical results. This is the impetus to broaden the number of patients eligible to benefit from adoptive immunotherapy such as to infuse third-party donor derived CAR(+)T-cells. This will overcome issues associated with (i) time to manufacture T-cells, (ii) cost to generate one product for one patient, (iii) inability to generate a product from lymphopenic patients or patient's immune cells fail to complete the manufacturing process, and (iv) heterogeneity of T-cell products produced for or from individual recipients. Establishing a biobank of allogeneic genetically modified immune cells from healthy third-party donors, which are cryopreserved and validated in advance of administration, will facilitate the centralizing manufacturing and widespread distribution of CAR(+)T-cells to multiple points-of-care in a timely manner. To achieve this, it is necessary to engineer an effective strategy to avoid deleterious allogeneic immune responses leading to toxicity and rejection. We review the strategies to establish "off-the-shelf" donor-derived biobanks for human application of CAR(+)T-cells as a drug.

摘要

相似文献

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本文引用的文献

[1]
Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy.

Clin Cancer Res. 2016-4-15

[2]
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Nat Rev Clin Oncol. 2016-6

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Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells.

Oncoimmunology. 2015-4-27

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Genetic editing of HLA expression in hematopoietic stem cells to broaden their human application.

Sci Rep. 2016-2-23

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CANCER IMMUNOTHERAPY. Baby's leukemia recedes after novel cell therapy.

Science. 2015-11-13

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Nat Rev Clin Oncol. 2016-1

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Mol Ther. 2016-3

[8]
CAR therapy: the CD19 paradigm.

J Clin Invest. 2015-9

[9]
Multiplex Genome-Edited T-cell Manufacturing Platform for "Off-the-Shelf" Adoptive T-cell Immunotherapies.

Cancer Res. 2015-7-16

[10]
The pharmacology of second-generation chimeric antigen receptors.

Nat Rev Drug Discov. 2015-7

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