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Bianca Zoennchen

Fraunhofer Institute for Cell Therapy and Immunology

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Alexander Arthur Wurm

National Center for Tumor Diseases

Gerhard Behre

Medizinische Hochschule Brandenburg Theodor Fontane

Stephan Fricke

Klinikum Chemnitz

Nadja Hilger

Fraunhofer Institute for Cell Therapy and Immunology

Claudia Mueller

Leipzig University

Lilly Stahl

Fraunhofer Institute for Cell Therapy and Immunology

Christoph Halbich

Fraunhofer Institute for Cell Therapy and Immunology

Anne Mueller

Fraunhofer Institute for Cell Therapy and Immunology

Sarah Dluczek

Fraunhofer Institute for Cell Therapy and Immunology

Anna Kretschmer

Fraunhofer Institute for Cell Therapy and Immunology

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Leipzig University

Fraunhofer Institute for Cell Therapy and Immunology

University Hospital Leipzig

Martin Luther University Halle-Wittenberg

University Hospital in Halle

TU Dresden

Fraunhofer Society

National Center for Tumor Diseases

University Hospital Carl Gustav Carus

Deutschen Konsortium für Translationale Krebsforschung

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Incubation of Immune Cell Grafts With MAX.16H5 IgG1 Anti-Human CD4 Antibody Prolonged Survival After Hematopoietic Stem Cell Transplantation in a Mouse Model for Fms Like Tyrosine Kinase 3 Positive Acute Myeloid Leukemia

Frontiers in Immunology (2018)

Nadja Hilger Claudia Mueller Lilly Stahl Anne Mueller Bianca Zoennchen

Despite the constant development of innovative therapeutic options for hematological malignancies, the gold-standard therapy regimen for curative treatment often includes allogeneic hematopoietic stem cell transplantation (HSCT). The graft-versus-leukemia effect (GVL) is one of the main therapeutic goals that arises from HSCT. On the other hand, graft-versus-host disease (GVHD) is still one of the main and most serious complications following allogeneic HSCT. In acute myeloid leukemia (AML), HSCT together with high-dose chemotherapy is used as a treatment option. An aggressive progression of the disease, a decreased response to treatment, and a poor prognosis are connected to internal tandem duplication (ITD) mutations in the FLT3 gene which affects around 30% of AML patients. In this study, C3H/HeN mice received an allogeneic graft together with 32D-FLT3ITD AML cells to induce acute GVHD and GVL. It was examined if pre-incubation of the graft with the anti-human CD4 antibody MAX.16H5 IgG1 prevented the development of GVHD and whether the GVL effect was impaired. Animals receiving grafts pre-incubated with the antibody together with FLT3ITD AML cells survived significantly longer than mice receiving untreated grafts. The MAX.16H5 antibody incubation did not affect the anti-tumor response mediated by allogeneic graft transplantation and the observed prolonged survival may allow an extended application of additional targeted treatment strategies.

10.3389/fimmu.2018.02408

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