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

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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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Authors and Affiliations

  1. Third Department of Internal Medicine, University of Ulm, Robert-Koch-Street 8, 89081, Ulm, Germany

    Li Li, Jochen Greiner, Mark Ringhoffer, Hartmut Döhner & Michael Schmitt

  2. Institute for Clinical Transfusion Medicine and Immunogenetics, University of Ulm, Ulm, Germany

    Peter Reinhardt, Anita Schmitt & Markus Wiesneth

  3. Institute of Pathology, University of Ulm, Ulm, Germany

    Thomas F. E. Barth

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  1. Li Li
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Correspondence to Michael Schmitt.

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Li, L., Reinhardt, P., Schmitt, A. et al. Dendritic cells generated from acute myeloid leukemia (AML) blasts maintain the expression of immunogenic leukemia associated antigens. Cancer Immunol Immunother 54, 685–693 (2005). https://doi.org/10.1007/s00262-004-0631-8

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  • DOI: https://doi.org/10.1007/s00262-004-0631-8

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