Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen–specific cytotoxic T lymphocytes

Cytotoxic T lymphocytes (CTLs) specific for hematopoietic-restricted minor histocompatibility antigens (mHags) are important reagents for adoptive immunotherapy of relapsed leukemia after allogeneic stem cell transplantation. However, expansion of these CTLs to therapeutic numbers is often hampered...

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Bibliographic Details
Published in:Blood 2004-07, Vol.104 (1), p.224-226
Main Authors: Oosten, Liesbeth E.M., Blokland, Els, van Halteren, Astrid G.S., Curtsinger, Julie, Mescher, Matthew F., Falkenburg, J. H. Frederik, Mutis, Tuna, Goulmy, Els
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Antigen Presentation - immunology
Antigen-Presenting Cells - physiology
Applied cell therapy and gene therapy
Biological and medical sciences
Cell Division - immunology
Cell Line
Clone Cells
Cytotoxicity, Immunologic
Dendritic Cells - immunology
Herpesvirus 4, Human - immunology
HLA-A2 Antigen - immunology
Humans
Interferon-gamma - biosynthesis
Medical sciences
Minor Histocompatibility Antigens - immunology
Oligopeptides - immunology
T-Lymphocytes, Cytotoxic - cytology
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - virology
T-Lymphocytes, Helper-Inducer - immunology
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
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Summary:Cytotoxic T lymphocytes (CTLs) specific for hematopoietic-restricted minor histocompatibility antigens (mHags) are important reagents for adoptive immunotherapy of relapsed leukemia after allogeneic stem cell transplantation. However, expansion of these CTLs to therapeutic numbers is often hampered by the limited supply of antigen-presenting cells (APCs). Therefore, we evaluated whether cell-sized latex beads coated with HLA/mHag complexes HLA-A2/HA-1 or HLA-A2/HA-2 and recombinant CD80 and CD54 molecules can replace professional APCs. The artificial antigen-presenting constructs (aAPCs) effectively stimulated HA-1– and HA-2–specific CTL clones as shown by ligand-specific expansion, cytokine production, and maintenance of cytotoxic activity, without alteration of CTL phenotype. Furthermore, HA-1–specific polyclonal CTL lines were enriched as efficiently by aAPCs as by autologous HA-1 peptide-pulsed dendritic cells. Thus, aAPCs coated with HLA/mHag complexes, CD80, and CD54 may serve as tools for in vitro enrichment of immunotherapeutic mHag-specific CTL lines.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2003-07-2461