PMID- 18418406
OWN - NLM
STAT- MEDLINE
DCOM- 20080826
LR  - 20130304
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 22
IP  - 7
DP  - 2008 Jul
TI  - HLA-DP as specific target for cellular immunotherapy in HLA class II-expressing 
      B-cell leukemia.
PG  - 1387-94
LID - 10.1038/leu.2008.90 [doi]
AB  - 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.
FAU - Rutten, C E
AU  - Rutten CE
AD  - Department of Hematology, Leiden University Medical Center, Leiden, The 
      Netherlands. c.e.rutten@lumc.nl
FAU - van Luxemburg-Heijs, S A P
AU  - van Luxemburg-Heijs SA
FAU - Griffioen, M
AU  - Griffioen M
FAU - Marijt, E W A
AU  - Marijt EW
FAU - Jedema, I
AU  - Jedema I
FAU - Heemskerk, M H M
AU  - Heemskerk MH
FAU - Posthuma, E F M
AU  - Posthuma EF
FAU - Willemze, R
AU  - Willemze R
FAU - Falkenburg, J H F
AU  - Falkenburg JH
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080417
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (HLA-DP Antigens)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPB1 antigen)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Female
MH  - Graft vs Host Disease/etiology
MH  - Graft vs Leukemia Effect
MH  - HLA-DP Antigens/*immunology
MH  - HLA-DP beta-Chains
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility Antigens Class II/*analysis
MH  - Histocompatibility Testing
MH  - Humans
MH  - *Immunotherapy, Adoptive
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/immunology/*therapy
MH  - Middle Aged
EDAT- 2008/04/18 09:00
MHDA- 2008/08/30 09:00
CRDT- 2008/04/18 09:00
PHST- 2008/04/18 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/04/18 09:00 [entrez]
AID - leu200890 [pii]
AID - 10.1038/leu.2008.90 [doi]
PST - ppublish
SO  - Leukemia. 2008 Jul;22(7):1387-94. doi: 10.1038/leu.2008.90. Epub 2008 Apr 17.