CD64-directed microtubule associated protein tau kills leukemic blasts ex vivo
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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
Stefan Barth, email: [email protected]
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
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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