6 results on '"Rian Bongaerts"'
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2. Phase I/II feasibility study evaluating the generation of leukemia-reactive cytotoxic T lymphocyte lines for treatment of patients with relapsed leukemia after allogeneic stem cell transplantation
- Author
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Erik Marijt, Amon Wafelman, Menno van der Hoorn, Cornelis van Bergen, Rian Bongaerts, Simone van Luxemburg-Heijs, Joost van den Muijsenberg, Judith Olde Wolbers, Nicole van der Werff, Roel Willemze, and Frederik Falkenburg
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background and Objectives Graft-versus-host-disease may be avoided and the likelihood of a graft-versus-leukemia reaction increased by infusion of in vitro-generated, leukemia-reactive, cytotoxic T lymphocyte (CTL) lines as treatment for patients with relapsed leukemia after allogeneic stem cell transplantation, instead of donor lymphocyte infusion. The aim of this phase I/II study was to assess the feasibility of large-scale in vitro generation of leukemia-reactive CTL for clinical use.Design and Methods Using a modified limiting dilution culture system donor T cells were stimulated with HLA-identical leukemic antigen-presenting cells. Feasibility experiments demonstrated that in 16 of 27 donor-recipient pairs tested a CTL line could be generated. Twelve of these 16 patients developed a relapse and for 11 of these 12 patients a CTL line was generated under Good Manufacturing Practice conditions.Results The CTL lines showed moderate to high cytotoxic activity against original recipient leukemic cells in vitro. Eight patients with a relapse received from one to seven CTL lines. One patient entered a complete remission after CTL infusion only, one entered a complete remission after combined CTL infusion and donor lymphocyte infusion, two patients had temporarily stable disease, and in four patients no response was observed.Interpretation and Conclusions Although the current procedure to generate these CTL lines is feasible, the strategy is logistically complex and time-consuming, and needs further improvement.
- Published
- 2007
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3. Generation and administration of HA-1-specific T-cell lines for the treatment of patients with relapsed leukemia after allogeneic stem cell transplantation: a pilot study
- Author
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Roel Willemze, Pauline Meij, J.H. Frederik Falkenburg, Linda Cox, Rian Bongaerts, Erik W.A. Marijt, Amon R. Wafelman, Inge Jedema, and Menno A. W. G. van der Hoorn
- Subjects
Oncology ,minor histocompatibility antigen ,medicine.medical_specialty ,Adoptive cell transfer ,T cell ,medicine.medical_treatment ,Pilot Projects ,Hematopoietic stem cell transplantation ,CD8-Positive T-Lymphocytes ,Minor Histocompatibility Antigens ,Recurrence ,allogeneic stem cell transplantation ,HA-1 ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,adoptive cellular immunotherapy ,Leukemia ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Adoptive Transfer ,Transplantation ,Treatment Outcome ,medicine.anatomical_structure ,CTL ,Immunology ,Bone marrow ,Original Articles and Brief Reports ,Stem cell ,business ,Oligopeptides ,CD8 - Abstract
Since HA-1-specific T cells have been shown to make a significant contribution to the clinical responses in patients with relapsed leukemia, we investigated the feasibility of adoptive transfer of in vitro induced HA-1-specific CD8 positive T cells to patients with relapsed leukemia after allogeneic stem cell transplantation. The in vitro generation of clinical grade HA-1-specific T-cell lines from HA-1 negative donors was seen to be feasible and 3 patients were treated with HA-1-specific T-cell lines. No toxicity after infusion was observed. Although in one patient, during a period of stable disease, HA-1-specific T cells could be detected in the peripheral blood and bone marrow, these patients had no clear clinical response.
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- 2012
4. Phase I/II feasibility study evaluating the generation of leukemia-reactive cytotoxic T lymphocyte lines for treatment of patients with relapsed leukemia after allogeneic stem cell transplantation
- Author
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Judith Olde Wolbers, Joost W. van den Muijsenberg, Cornelis A.M. van Bergen, Nicole M. van der Werff, Roel Willemze, Frederik Falkenburg, Rian Bongaerts, Menno A. W. G. van der Hoorn, Amon R. Wafelman, Simone A.P. van Luxemburg-Heijs, and Erik W.A. Marijt
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Antigen-Presenting Cells ,Immunotherapy, Adoptive ,Donor lymphocyte infusion ,Recurrence ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Cytotoxic T cell ,Child ,In Situ Hybridization, Fluorescence ,Leukemia ,Hematology ,business.industry ,Immunotherapy ,Middle Aged ,medicine.disease ,Transplantation ,CTL ,Phenotype ,Treatment Outcome ,Immunology ,Cancer research ,Female ,Stem cell ,business ,Stem Cell Transplantation ,T-Lymphocytes, Cytotoxic - Abstract
Graft-versus-host-disease may be avoided and the likelihood of a graft-versus-leukemia reaction increased by infusion of in vitro generated, leukemia-reactive, cytotoxic T lymphocyte (CTL) lines as treatment for patients with relapsed leukemia after allogeneic stem cell transplantation, instead of donor lymphocyte infusion. The aim of this study phase I/II study was to assess the feasibility of large-scale in vitro generation of leukemia-reactive CTL for clinical use.Using a modified limiting dilution culture system donor T cells were stimulated with HLA-identical leukemic antigen presenting cells. Feasibility experiments demonstrated that in 16 of 27 donor-recipient pairs tested a CTL line could be generated. Twelve of these 16 patients developed a relapse and for 11 of these 12 patients a CTL line was generated under Good Manufacturing Practice conditions.The CTL lines showed moderate to high cytotoxic activity against original recipient leukemic cells in vitro. Eight patients with a relapse received from one to seven CTL lines. One patient entered a complete remission after CTL infusion only, one entered a complete remission after combined CTL infusion and donor lymphocyte infusion, two patients had temporarily stable disease, and in four patients no response was observed.Although the current procedure to generate these CTL lines is feasible, the strategy is logistically complex and time-consuming, and needs further improvement. Key words: cellular immunotherapy, CTL, leukemia, allogeneic stem cell transplantation.
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- 2007
5. The progenitor cell inhibition assay to measure the anti-leukemic reactivity of T cell clones against acute and chronic myeloid leukemia
- Author
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C.A.M. van Bergen, Roelof Willemze, J.H.F. Falkenburg, S.A.P. van Luxemburg-Heijs, Rian Bongaerts, and M.A.W.G. van der Hoorn
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Cytotoxicity, Immunologic ,T cell ,Antigens, CD34 ,Jurkat cells ,Immunotherapy, Adoptive ,General Biochemistry, Genetics and Molecular Biology ,Colony-Forming Units Assay ,Antigen ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Tumor Cells, Cultured ,Cytotoxic T cell ,Humans ,Progenitor cell ,Molecular Biology ,Interleukin 3 ,Dose-Response Relationship, Drug ,Chemistry ,medicine.disease ,Molecular biology ,Clone Cells ,Haematopoiesis ,Leukemia ,medicine.anatomical_structure ,Leukemia, Myeloid ,Acute Disease ,Neoplastic Stem Cells ,Cytokines ,Cell Division ,T-Lymphocytes, Cytotoxic ,Thymidine - Abstract
Adoptive immunotherapy with donor T lymphocytes may be used as a treatment for relapsed leukemia after allogeneic hematopoietic stem cell transplantation (SCT). In vitro selected and expanded anti-leukemic T cells may be more effective in inducing a response in vivo. To identify the anti-leukemic reactivity of in vitro generated T cells, standard target cell read-out assays like the 51Cr-release assay are not always appropriate. We developed an assay in which the ability of T cells to antigen specifically inhibit the in vitro growth of leukemic progenitor cells in the presence of cytokines can be measured. This assay allows the evaluation of the cytolytic or suppressive potential of leukemia reactive T cells for prolonged periods of time. The assay is based on inhibition of [3H]thymidine incorporation by the leukemic progenitor cells induced by multiple hematopoietic growth factors. T cell clones with a known specificity were used to compare the analytic potential of the new assay with those of other cytotoxicity assays. Based on the results of the T cell clones, a modification of a limiting dilution assay was developed to identify anti-leukemic allogeneic T cells in HLA identical donor–recipient combinations selected on their ability to inhibit the in vitro growth of CML or AML progenitor cells, to be used for the generation of leukemia-reactive CTL lines for clinical use.
- Published
- 2003
6. Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes
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Ellie Lurvink, P. M. C. Kluck, Menno A. W. G. van der Hoorn, Willem E. Fibbe, J.H. Frederik Falkenburg, Cornelis A.M. van Bergen, Rian Bongaerts, Willem M. Smit, James E. Landegent, Roel Willemze, Hanneke C. Kluin-Nelemans, Peter Joosten, and Amon R. Wafelman
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Acute leukemia ,Myeloid ,business.industry ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Donor lymphocyte infusion ,CTL ,Leukemia ,medicine.anatomical_structure ,hemic and lymphatic diseases ,medicine ,Progenitor cell ,business ,Chronic myelogenous leukemia - Abstract
Relapse of chronic myeloid leukemia (CML) in chronic phase after allogeneic stem cell transplantation (SCT) can be successfully treated by donor lymphocyte infusion (DLI). However, relapse of accelerated phase CML, blast crisis, or acute leukemia after allogeneic SCT are resistant to DLI in the majority of cases. In vitro-selected and expanded leukemia-reactive T-cell lines may be more effective in inducing an antileukemic response in vivo. To treat a patient with accelerated phase CML after allogeneic SCT, leukemia-reactive cytotoxic T-lymphocyte (CTL) lines were generated from her HLA-identical donor. Using a modification of a limiting dilution assay, T cells were isolated from the donor, selected based on their ability to inhibit the in vitro growth of CML progenitor cells, and subsequently expanded in vitro to generate CTL lines. Three CTL lines were generated that lysed the leukemic cells from the patient and inhibited the growth of leukemic progenitor cells. The CTL did not react with lymphocytes from donor or recipient and did not affect donor hematopoietic progenitor cells. The 3 leukemia-reactive CTL lines were infused at 5-week intervals at a cumulative dose of 3.2 × 109 CTL. Shortly after the third infusion, complete eradication of the leukemic cells was observed, as shown by cytogenetic analysis, fluorescence in situ hybridization, molecular analysis of BCR/ABL-mRNA, and chimerism studies. These results show that in vitro cultured leukemia-reactive CTL lines selected on their ability to inhibit the proliferation of leukemic progenitor cells in vitro can be successfully applied to treat accelerated phase CML after allogeneic SCT.
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