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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 7/2005

01-07-2005 | Original Article

Dendritic cells generated from acute myeloid leukemia (AML) blasts maintain the expression of immunogenic leukemia associated antigens

Authors: Li Li, Peter Reinhardt, Anita Schmitt, Thomas F. E. Barth, Jochen Greiner, Mark Ringhoffer, Hartmut Döhner, Markus Wiesneth, Michael Schmitt

Published in: Cancer Immunology, Immunotherapy | Issue 7/2005

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Abstract

Recently, the focus is on new specific immunotherapies for AML such as cellular therapies employing dendritic cells (DCs) generated from AML blasts. AML-DCs express constitutionally leukemia-associated antigens (LAAs) present in AML blasts they are generated from. Here we investigated whether the generation of AML-DCs would alter the expression level of LAAs. Moreover, we evaluated the presence of HLA and costimulatory molecules on AML blasts versus AML-DCs. Quantitative real-time polymerase chain reaction (PCR) was performed for the following LAAs: preferentially expressed antigen in melanoma (PRAME), the receptor for hyaluronic acid mediated motility (RHAMM/CD168), Wilms’ tumor gene 1 (WT-1) and proteinase 3. The expression of HLA-ABC, HLA-DR, CD40, CD80, CD83 and CD86 was evaluated by flow cytometry. RHAMM protein expression was evaluated by immunocytochemistry, recognition of AML-DCs by PRAME epitope-specific T cells was evaluated in a chromium-release assay. Quantitative real-time PCR for AML-DCs versus AML blasts showed an alteration in mRNA expression of LAAs. An elevated PCR signal for PRAME was detected in 7/12 AML-DC preparations. 6/12 AML-DC preparations showed a significant upregulation of the PCR signal for RHAMM. A stronger WT-1 and proteinase-3 signal was observed in PCR for only 2/12 and 1/12 AML-DCs , respectively. All preparations showed a strong expression of at least one of the LAAs examined. As demonstrated by flow cytometry, AML-DCs strongly upregulated costimulatory molecules like CD40 and CD80 in comparison with AML blasts. AML-DCs tested positive for RHAMM protein. PRAME positive AML-DCs were recognized by specific T cells. AML-DCs might constitute a powerful tool in immunotherapy for AML. Real-time PCR allows a quick and quantitative assessment of immunologically relevant LAA expression with only 105 DCs and might be helpful for the decision whether the AML-DC vaccination strategy is favourable or not.
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Metadata
Title
Dendritic cells generated from acute myeloid leukemia (AML) blasts maintain the expression of immunogenic leukemia associated antigens
Authors
Li Li
Peter Reinhardt
Anita Schmitt
Thomas F. E. Barth
Jochen Greiner
Mark Ringhoffer
Hartmut Döhner
Markus Wiesneth
Michael Schmitt
Publication date
01-07-2005
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 7/2005
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-004-0631-8

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