| Antigen-independent and antigen-dependent methods to numerically expand CD19-specific CD8+ T cells. | |
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MedLine Citation:
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PMID: 17588477 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Preclinical and clinical trials are investigating the potential of T cells genetically modified to express a first-generation CD19-specific chimeric antigen receptor (CAR), designated CD19R, for adoptive immunotherapy of B-lineage leukemias and lymphomas. Currently, our genetically modified CD19-specific CD8+ (CD19R+CD8+) T cells are expanded ex vivo using a rapid expansion protocol (REP) to clinically meaningful numbers after antigen-independent activation with anti-CD3epsilon and recombinant human interleukin-2 on a double-cell feeder-layer of gamma-irradiated allogeneic peripheral blood mononuclear cells and a lymphoblastoid cell line. We now compare the ability of the REP with CD19-dependent numerical expansion using CD19+ artificial antigen-presenting cells to propagate CD19R+CD8+ T cells. MATERIALS AND METHODS: We evaluated long-term (28 days) propagation, CD19R CAR expression, and cytolytic activity of CD19R+CD8+ T cells expanded by either a REP or an antigen expansion protocol (AEP) using K562-derived artificial antigen-presenting cells coexpressing CD19 antigen and two T-cell costimulatory molecules (4-1BB ligand and major histocompatibility class I-related chains A) in the presence of exogenous recombinant human interleukin-2 and recombinant human interleukin-15. RESULTS: Populations of CD19R+CD8+ T cells could be numerically expanded on AEP to meet anticipated clinical need. The AEP was superior to REP, as this method selected for an outgrowth of T cells with increased CD19R CAR expression and improved redirected cytolytic activity. CONCLUSION: Robust propagation of CD19R+CD8+ T cells achieved by AEP supports qualifying this cell line for use in current good manufacturing practices for CAR+ T cells as an alternative to REP for adoptive immunotherapy clinical trials. |
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Authors:
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Tontanai Numbenjapon; Lisa M Serrano; Wen-Chung Chang; Stephen J Forman; Michael C Jensen; Laurence J N Cooper |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental hematology Volume: 35 ISSN: 0301-472X ISO Abbreviation: Exp. Hematol. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-25 Completed Date: 2007-08-02 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 0402313 Medline TA: Exp Hematol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1083-90 Citation Subset: IM |
Affiliation:
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Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, Duarte, Calif., USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigen-Presenting Cells
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physiology Antigens, CD19 / analysis, physiology* CD8-Positive T-Lymphocytes / immunology, physiology* Cell Line, Tumor Humans Immunotherapy, Adoptive Receptors, Antigen, T-Cell / analysis |
| Grant Support | |
ID/Acronym/Agency:
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CA003572/CA/NCI NIH HHS; CA107399/CA/NCI NIH HHS; CA30206/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD19; 0/Receptors, Antigen, T-Cell |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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