Document Detail


Antigen-independent and antigen-dependent methods to numerically expand CD19-specific CD8+ T cells.
MedLine Citation:
PMID:  17588477     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Tontanai Numbenjapon; Lisa M Serrano; Wen-Chung Chang; Stephen J Forman; Michael C Jensen; Laurence J N Cooper
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental hematology     Volume:  35     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-25     Completed Date:  2007-08-02     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1083-90     Citation Subset:  IM    
Affiliation:
Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, Duarte, Calif., USA.
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MeSH Terms
Descriptor/Qualifier:
Antigen-Presenting Cells / 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:
CA003572/CA/NCI NIH HHS; CA107399/CA/NCI NIH HHS; CA30206/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD19; 0/Receptors, Antigen, T-Cell

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