title: CD64-directed microtubule associated protein tau kills leukemic blasts ex vivo.
abstract: Fc gamma receptor I (FcγRI, CD64) is a well-known target antigen for passive immunotherapy against acute myeloid leukemia and chronic myelomonocytic leukemia. We recently reported the preclinical immunotherapeutic potential of microtubule associated protein tau (MAP) against a variety of cancer types including breast carcinoma and Hodgkin's lymphoma. Here we demonstrate that the CD64-directed human cytolytic fusion protein H22(scFv)-MAP kills ex vivo 15-50% of CD64+ leukemic blasts derived from seven myeloid leukemia patients. Furthermore, in contrast to the nonspecific cytostatic agent paclitaxel, H22(scFv)-MAP showed no cytotoxicity towards healthy CD64+ PBMC-derived cells and macrophages. The targeted delivery of this microtubule stabilizing agent therefore offers a promising new strategy for specific treatment of CD64+ leukemia.
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.
authors: Radoslav
authors: R
authors: Mladenov
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.
authors: Dmitrij
authors: D
authors: Hristodorov
authors: Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany.
authors: Christian
authors: C
authors: Cremer
authors: Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany.
authors: Gerrit
authors: G
authors: Gresch
authors: Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany.
authors: Elena
authors: E
authors: Grieger
authors: Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany.
authors: Lea
authors: L
authors: Schenke
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.
authors: Diana
authors: D
authors: Klose
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.
authors: Manal
authors: M
authors: Amoury
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.
authors: Mira
authors: M
authors: Woitok
authors: Department of Haematology and Oncology (Internal Medicine IV), RWTH Aachen University Hospital, Aachen, Germany.
authors: Edgar
authors: E
authors: Jost
authors: Department of Haematology and Oncology (Internal Medicine IV), RWTH Aachen University Hospital, Aachen, Germany.
authors: Tim H
authors: TH
authors: Brümmendorf
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.|Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany.
authors: Rolf
authors: R
authors: Fendel
authors: Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany.|Institute of Molecular Biotechnology (Biology VII), RWTH Aachen University, Aachen, Germany.
authors: Rainer
authors: R
authors: Fischer
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.|Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany.
authors: Christoph
authors: C
authors: Stein
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.
authors: Theo
authors: T
authors: Thepen
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany.|Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany.|South African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
authors: Stefan
authors: S
authors: Barth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute; D008297:Male; D008869:Microtubule-Associated Proteins / Q000494:pharmacology*; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C489017:FCGR1A protein, human; D000922:Immunotoxins; D008869:Microtubule-Associated Proteins; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins
keywords: Fc-gamma receptor (CD64); cytolytic fusion proteins; immunotherapy; microtubule associated protein tau (MAP); myeloid leukemia