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HLA-DP as specific target for cellular immunotherapy in HLA class II-expressing B-cell leukemia. 2008

C E Rutten, and S A P van Luxemburg-Heijs, and M Griffioen, and E W A Marijt, and I Jedema, and M H M Heemskerk, and E F M Posthuma, and R Willemze, and J H F Falkenburg
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands. c.e.rutten@lumc.nl

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.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D005260 Female Females
D006086 Graft vs Host Disease The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION. Graft-Versus-Host Disease,Homologous Wasting Disease,Runt Disease,Graft-vs-Host Disease,Disease, Graft-Versus-Host,Disease, Graft-vs-Host,Disease, Homologous Wasting,Disease, Runt,Diseases, Graft-Versus-Host,Diseases, Graft-vs-Host,Graft Versus Host Disease,Graft-Versus-Host Diseases,Graft-vs-Host Diseases
D006650 Histocompatibility Testing Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed) Crossmatching, Tissue,HLA Typing,Tissue Typing,Crossmatchings, Tissue,HLA Typings,Histocompatibility Testings,Testing, Histocompatibility,Testings, Histocompatibility,Tissue Crossmatching,Tissue Crossmatchings,Tissue Typings,Typing, HLA,Typing, Tissue,Typings, HLA,Typings, Tissue
D006682 HLA-DP Antigens A group of the D-related HLA antigens (human) found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases. HLA-PL Antigens,HLA-SB Antigens,HLA-DP,HLA-PL,HLA-SB,Antigens, HLA-DP,Antigens, HLA-PL,Antigens, HLA-SB,HLA DP Antigens,HLA PL Antigens,HLA SB Antigens
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000949 Histocompatibility Antigens Class II Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen. Antigens, Immune Response,Class II Antigens,Class II Histocompatibility Antigen,Class II Major Histocompatibility Antigen,Ia Antigens,Ia-Like Antigen,Ia-Like Antigens,Immune Response Antigens,Immune-Associated Antigens,Immune-Response-Associated Antigens,MHC Class II Molecule,MHC II Peptide,Class II Antigen,Class II Histocompatibility Antigens,Class II MHC Proteins,Class II Major Histocompatibility Antigens,Class II Major Histocompatibility Molecules,I-A Antigen,I-A-Antigen,IA Antigen,MHC Class II Molecules,MHC II Peptides,MHC-II Molecules,Antigen, Class II,Antigen, I-A,Antigen, IA,Antigen, Ia-Like,Antigens, Class II,Antigens, Ia,Antigens, Ia-Like,Antigens, Immune-Associated,Antigens, Immune-Response-Associated,I A Antigen,II Peptide, MHC,Ia Like Antigen,Ia Like Antigens,Immune Associated Antigens,Immune Response Associated Antigens,MHC II Molecules,Molecules, MHC-II,Peptide, MHC II,Peptides, MHC II
D015451 Leukemia, Lymphocytic, Chronic, B-Cell A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease. B-Cell Leukemia, Chronic,B-Lymphocytic Leukemia, Chronic,Chronic Lymphocytic Leukemia,Leukemia, B-Cell, Chronic,Leukemia, Lymphocytic, Chronic,Lymphocytic Leukemia, Chronic, B-Cell,Lymphoma, Small Lymphocytic,B-Cell Chronic Lymphocytic Leukemia,B-Cell Malignancy, Low-Grade,Diffuse Well-Differentiated Lymphocytic Lymphoma,Disrupted In B-Cell Malignancy,Leukemia, B Cell, Chronic,Leukemia, Chronic Lymphatic,Leukemia, Chronic Lymphocytic,Leukemia, Chronic Lymphocytic, B-Cell,Leukemia, Lymphoblastic, Chronic,Leukemia, Lymphocytic, Chronic, B Cell,Lymphoblastic Leukemia, Chronic,Lymphocytic Leukemia, Chronic,Lymphocytic Leukemia, Chronic, B Cell,Lymphocytic Lymphoma,Lymphocytic Lymphoma, Diffuse, Well Differentiated,Lymphocytic Lymphoma, Diffuse, Well-Differentiated,Lymphocytic Lymphoma, Well Differentiated,Lymphocytic Lymphoma, Well-Differentiated,Lymphoma, Lymphocytic,Lymphoma, Lymphocytic, Diffuse, Well Differentiated,Lymphoma, Lymphocytic, Diffuse, Well-Differentiated,Lymphoma, Lymphocytic, Well Differentiated,Lymphoma, Lymphocytic, Well-Differentiated,Lymphoma, Lymphoplasmacytoid, CLL,Lymphoma, Small Lymphocytic, Plasmacytoid,Lymphoma, Small-Cell,Lymphoplasmacytoid Lymphoma, CLL,Small-Cell Lymphoma,B Cell Chronic Lymphocytic Leukemia,B Cell Leukemia, Chronic,B Cell Malignancy, Low Grade,B Lymphocytic Leukemia, Chronic,B-Cell Leukemias, Chronic,B-Cell Malignancies, Low-Grade,B-Lymphocytic Leukemias, Chronic,CLL Lymphoplasmacytoid Lymphoma,CLL Lymphoplasmacytoid Lymphomas,Chronic B-Cell Leukemia,Chronic B-Cell Leukemias,Chronic B-Lymphocytic Leukemia,Chronic B-Lymphocytic Leukemias,Chronic Lymphatic Leukemia,Chronic Lymphatic Leukemias,Chronic Lymphoblastic Leukemia,Chronic Lymphoblastic Leukemias,Chronic Lymphocytic Leukemias,Diffuse Well Differentiated Lymphocytic Lymphoma,Disrupted In B Cell Malignancy,Leukemia, Chronic B-Cell,Leukemia, Chronic B-Lymphocytic,Leukemias, Chronic B-Cell,Leukemias, Chronic B-Lymphocytic,Leukemias, Chronic Lymphatic,Leukemias, Chronic Lymphoblastic,Low-Grade B-Cell Malignancies,Low-Grade B-Cell Malignancy,Lymphatic Leukemia, Chronic,Lymphatic Leukemias, Chronic,Lymphoblastic Leukemias, Chronic,Lymphocytic Leukemias, Chronic,Lymphocytic Lymphoma, Small,Lymphocytic Lymphomas,Lymphocytic Lymphomas, Small,Lymphocytic Lymphomas, Well-Differentiated,Lymphoma, CLL Lymphoplasmacytoid,Lymphoma, Small Cell,Lymphoma, Well-Differentiated Lymphocytic,Lymphomas, CLL Lymphoplasmacytoid,Lymphomas, Lymphocytic,Lymphomas, Small Lymphocytic,Lymphomas, Small-Cell,Lymphomas, Well-Differentiated Lymphocytic,Lymphoplasmacytoid Lymphomas, CLL,Malignancies, Low-Grade B-Cell,Malignancy, Low-Grade B-Cell,Small Cell Lymphoma,Small Lymphocytic Lymphoma,Small Lymphocytic Lymphomas,Small-Cell Lymphomas,Well-Differentiated Lymphocytic Lymphoma,Well-Differentiated Lymphocytic Lymphomas
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016219 Immunotherapy, Adoptive Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314) Adoptive Cellular Immunotherapy,Adoptive Immunotherapy,CAR T-Cell Therapy,Cellular Immunotherapy, Adoptive,Chimeric Antigen Receptor Therapy,Immunotherapy, Adoptive Cellular,Adoptive Cellular Immunotherapies,Adoptive Immunotherapies,CAR T Cell Therapy,CAR T-Cell Therapies,Cellular Immunotherapies, Adoptive,Immunotherapies, Adoptive,Immunotherapies, Adoptive Cellular,T-Cell Therapies, CAR,T-Cell Therapy, CAR,Therapies, CAR T-Cell,Therapy, CAR T-Cell

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