Prevention of graft-versus-host-disease with preserved graft-versus-leukemia-effect by ex vivo and in vivo modulation of CD4(+) T-cells

Autor: Stephan Fricke, Gerhard Behre, Nadja Hilger, Christopher Oelkrug, Christian Fricke, Frank Emmrich, Andreas Boldt, Ulrich Sack, Uta Schönfelder, Peter Ruschpler
Rok vydání: 2013
Předmět:
CD4-Positive T-Lymphocytes
Graft-vs-Leukemia Effect
medicine.medical_treatment
Graft vs Host Disease
Graft vs Leukemia Effect
Mice
Transgenic
Hematopoietic stem cell transplantation
Immune tolerance
Immunomodulation
Cellular and Molecular Neuroscience
Mice
immune system diseases
medicine
Immune Tolerance
Animals
Humans
Transplantation
Homologous
Molecular Biology
Cells
Cultured
Antilymphocyte Serum
Pharmacology
Transplantation Chimera
Leukemia
business.industry
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cell
Cell Biology
medicine.disease
Hematopoietic Stem Cells
Survival Analysis
Transplantation
Disease Models
Animal
surgical procedures
operative
Graft-versus-host disease
medicine.anatomical_structure
Immunoglobulin G
Immunology
Molecular Medicine
business
Ex vivo
Whole-Body Irradiation
Zdroj: Cellular and molecular life sciences : CMLS. 71(11)
ISSN: 1420-9071
Popis: This is the first report showing that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG1 simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect, GvL) and the long-term suppression of the deleterious side effect Graft-versus-host-disease (GvHD). To distinguish and consolidate GvL from GvHD, the anti-human CD4 antibody MAX16.H5 IgG1 was tested in murine GvHD and tumor models. The survival rate was significantly increased in recipients receiving a MAX.16H5 IgG1 short-term (2 h) pre-incubated graft even when tumor cells were co-transplanted or when recipient mice were treated by MAX.16H5 IgG1 before transplantation. After engraftment, regulatory T-cells are generated only supporting the GvL effect. It was also possible to transfer the immune tolerance from GvHD-free recipient chimeras into third party recipient mice without the need of reapplication of MAX.16H5 IgG1 anti-human CD4 antibodies. These findings are also benefical for patients with leukemia when no matched related or unrelated donor is available and provides a safer allogeneic HSCT, which is more effective against leukemia. It also facilitates allogeneic (stem) cell transplantations for other indications (e.g., autoimmune-disorders).
Databáze: OpenAIRE
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