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

// Radoslav Mladenov 1 , Dmitrij Hristodorov 1 , Christian Cremer 2 , Gerrit Gresch 2 , Elena Grieger 2 , Lea Schenke 2 , Diana Klose 1 , Manal Amoury 1 , Mira Woitok 1 , Edgar Jost 3 , Tim H. Brummendorf 3 , Rolf Fendel 1, 2 , Rainer Fischer 2, 4 , Christoph Stein 1, 2 , Theo Thepen 1, * , Stefan Barth 1, 2, 5, * 1 Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen, Germany 2 Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital, RWTH Aachen University, Aachen, Germany 3 Department of Haematology and Oncology (Internal Medicine IV), RWTH Aachen University Hospital, Aachen, Germany 4 Institute of Molecular Biotechnology (Biology VII), RWTH Aachen University, Aachen, Germany 5 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 * 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 m icrotubule a ssociated p rotein 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.