Oncotarget

Research Papers:

CD64-directed microtubule associated protein tau kills leukemic blasts ex vivo

Radoslav Mladenov, Dmitrij Hristodorov, Christian Cremer, Gerrit Gresch, Elena Grieger, Lea Schenke, Diana Klose, Manal Amoury, Mira Woitok, Edgar Jost, Tim H. Brümmendorf, Rolf Fendel, Rainer Fischer, Christoph Stein, Theo Thepen and Stefan Barth _

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Oncotarget. 2016; 7:67166-67174. https://doi.org/10.18632/oncotarget.11568

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Abstract

Radoslav Mladenov1, Dmitrij Hristodorov1, Christian Cremer2, Gerrit Gresch2, Elena Grieger2, Lea Schenke2, Diana Klose1, Manal Amoury1, Mira Woitok1, Edgar Jost3, Tim H. Brümmendorf3, Rolf Fendel1,2, Rainer Fischer2,4, Christoph Stein1,2, Theo Thepen1,*, Stefan Barth1,2,5,*

1Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany

2Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany

3Department of Haematology and Oncology (Internal Medicine IV), RWTH Aachen University Hospital, Aachen, Germany

4Institute of Molecular Biotechnology (Biology VII), RWTH Aachen University, Aachen, Germany

5South 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

*Shared authorship

Correspondence to:

Stefan Barth, email: stefan.barth@uct.ac.za

Keywords: immunotherapy, myeloid leukemia, cytolytic fusion proteins, Fc-gamma receptor (CD64), microtubule associated protein tau (MAP)

Received: March 14, 2016    Accepted: August 11, 2016    Published: August 24, 2016

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.


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