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

: Mladenov, R.; Hristodorov, D.; Cremer, C.; Gresch, G.; Grieger, G.; Schenke, L.; Klose, D.; Amoury, M.; Woitok, M.; Jost, E.; Brümmerdorf, T.H.; Fendel, R.; Fischer, R.; Stein, C.; Thepen, T.; Barth, S.

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OncoTarget 7 (2016), Nr.41, S.67166-67174
ISSN: 1949-2553
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IME ()

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.