دورية أكاديمية
Manufacture of Chimeric Antigen Receptor T Cells from Mobilized Cyropreserved Peripheral Blood Stem Cell Units Depends on Monocyte Depletion.
| العنوان: | Manufacture of Chimeric Antigen Receptor T Cells from Mobilized Cyropreserved Peripheral Blood Stem Cell Units Depends on Monocyte Depletion. |
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| المؤلفون: | Künkele A; Department of Pediatric Oncology and Hematology, Charité University Medical Center, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington. Electronic address: Annette.kuenkele@charite.de., Brown C; Seattle Children's Research Institute, Seattle, Washington., Beebe A; Seattle Children's Research Institute, Seattle, Washington., Mgebroff S; Seattle Children's Research Institute, Seattle, Washington., Johnson AJ; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington., Taraseviciute A; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington; Fred Hutchinson Cancer Research Center, Seattle, Washington; Seattle Children's Hospital, Department of Pediatrics, University of Washington, Seattle, Washington., Rolczynski LS; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington., Chang CA; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington., Finney OC; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington., Park JR; Fred Hutchinson Cancer Research Center, Seattle, Washington; Seattle Children's Hospital, Department of Pediatrics, University of Washington, Seattle, Washington., Jensen MC; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington; Fred Hutchinson Cancer Research Center, Seattle, Washington; Seattle Children's Hospital, Department of Pediatrics, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington. |
| المصدر: | Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2019 Feb; Vol. 25 (2), pp. 223-232. Date of Electronic Publication: 2018 Oct 10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Carden Jennings Publishing Country of Publication: United States NLM ID: 9600628 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-6536 (Electronic) Linking ISSN: 10838791 NLM ISO Abbreviation: Biol Blood Marrow Transplant Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Charlottesville, VA : Carden Jennings Publishing Original Publication: Charlottesville, VA : Kluge Carden Jennings Publishing, Co., Ltd., [1995- |
| مواضيع طبية MeSH: | Adoptive Transfer* , Cryopreservation* , Hematopoietic Stem Cell Mobilization* , Neuroblastoma*/immunology , Neuroblastoma*/pathology , Neuroblastoma*/therapy , Peripheral Blood Stem Cells*/immunology , Peripheral Blood Stem Cells*/pathology, Receptors, Chimeric Antigen/*immunology, Animals ; Cell Line, Tumor ; Female ; Humans ; Male ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Retrospective Studies ; Xenograft Model Antitumor Assays |
| مستخلص: | Cytotoxic chemotherapy and radiation can render lymphocyte repertoires qualitatively and quantitatively defective. Thus, heavily treated patients are often poor candidates for the manufacture of autologous chimeric antigen receptor (CAR)-T cell products. In the United States and Europe, children with high-risk neuroblastoma undergo apheresis early in the course of treatment to collect peripheral blood stem cells (PBSCs) for cryopreservation in preparation for high-dose chemotherapy followed by autologous stem cell rescue. Here, we investigate whether these cryopreserved chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCs can serve as starting material for CAR-T cell manufacturing. We evaluated T cell precursor subsets in cryopreserved PBSC units from 8 patients with neuroblastoma using fluorescent activated cell sorting-based analysis. Every cryopreserved unit collected early in treatment contained both CD4 and CD8 precursors with significant numbers of naïve and central memory precursors. Significant numbers of Ki67 + /PD1 + T cells were detected, presumably the result of chemotherapy-induced lymphopenia and subsequent homeostatic proliferation. Cryopreserved PBSC units containing 56 to 112 × 10 6 T cells were amenable to immunomagnetic selection, CD3 × 28 bead activation, lentiviral transduction, and cytokine-driven expansion, provided that CD14 monocytes were depleted before the initiation of cultures. Second- and third-generation CD171 CAR + CD4 and CD8 effector cells derived from cryopreserved units displayed antineuroblastoma lytic potency and cytokine secretion comparable to those derived from a healthy donor and mediated in vivo antitumor regression in NSG mice. We conclude that cryopreserved PBSCs procured via standard methods during early treatment can serve as an alternative starting source for CAR-T cell manufacturing, extending the options for heavily treated patients. (Copyright © 2018. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Autologous cryopreserved G-CSF-mobilized PBSCs; CAR-T cell manufacturing; CD14 depletion |
| المشرفين على المادة: | 0 (Receptors, Chimeric Antigen) |
| تواريخ الأحداث: | Date Created: 20181014 Date Completed: 20191224 Latest Revision: 20210803 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.bbmt.2018.10.004 |
| PMID: | 30315942 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1523-6536 |
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| DOI: | 10.1016/j.bbmt.2018.10.004 |