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

Leukemia. 2008 Jul;22(7):1387-94. doi: 10.1038/leu.2008.90. Epub 2008 Apr 17.

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-gamma (IFN-gamma) 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Leukemia Effect
  • HLA-DP Antigens / immunology*
  • HLA-DP beta-Chains
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Antigens Class II / analysis*
  • Histocompatibility Testing
  • Humans
  • Immunotherapy, Adoptive*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Middle Aged

Substances

  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • Histocompatibility Antigens Class II