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Immunology

HLA-DP as specific target for cellular immunotherapy in HLA class II-expressing B-cell leukemia

Leukemia volume 22, pages 1387–1394 (2008)Cite this article

Abstract

Mismatching for human leukocyte antigen (HLA)-DPB1 in unrelated donor hematopoietic stem cell transplantation (URD-SCT) has been associated with a decreased risk of disease relapse, indicating that HLA-DP may represent a target for graft-versus-leukemia (GVL) reactivity in HLA class II-expressing hematological malignancies. To investigate whether HLA-DP-specific T cells could mediate GVL reactivity following HLA-DPB1-mismatched URD-SCT and donor lymphocyte infusion (DLI), we analyzed the immune response in a patient with leukemic lymphoplasmacytic lymphoma responding to DLI without graft-versus-host disease. The emergence of leukemia-reactive CD4+ T cells during the clinical immune response was demonstrated by interferon-γ (IFN-γ) enzyme-linked immunosorbent spot(ELISPOT)analysis. Following clonal isolation of these leukemia-reactive CD4+ T cells, blocking studies, panel studies and retroviral transduction experiments of both mismatched HLA-DPB1 alleles identified HLA-DPB1*0201 and HLA-DPB1*0301 as the targets of this immune response. The HLA-DPB1-specific CD4+ T-cell clones were capable of recognizing and lysing several HLA-DP-expressing myeloid and lymphoid hematological malignant cells. Since HLA-DP expression is mainly restricted to hematopoietic cells, HLA-DP may be used as a specific target for immunotherapy following T-cell-depleted URD-SCT. Therefore, in patients with HLA class II-expressing hematological malignancies HLA-DP-mismatched SCT may be preferable over fully matched SCT allowing DLI to induce a GVL effect.

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Acknowledgements

We thank E van der Meijden for technical assistance with molecular work and R van der Linden and G de Roo for technical assistance with the flow cytometric isolation. We also thank Dr A Mulder for kindly providing the moAbs used for blocking experiments in this study. This work has been supported by a grant from the Dutch Cancer Society (grant no. 05-3267) and by a grant from the European Union 6th Framework Programme (Allostem project no. 503319).

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Authors and Affiliations

  1. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    C E Rutten, S A P van Luxemburg-Heijs, M Griffioen, E W A Marijt, I Jedema, M H M Heemskerk, E F M Posthuma, R Willemze & J H F Falkenburg

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  1. C E Rutten
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  2. S A P van Luxemburg-Heijs
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Correspondence to C E Rutten.

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Rutten, C., van Luxemburg-Heijs, S., Griffioen, M. et al. HLA-DP as specific target for cellular immunotherapy in HLA class II-expressing B-cell leukemia. Leukemia 22, 1387–1394 (2008). https://doi.org/10.1038/leu.2008.90

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