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

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 type...

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Detalles Bibliográficos
Autores principales: Mladenov, Radoslav, Hristodorov, Dmitrij, Cremer, Christian, Gresch, Gerrit, Grieger, Elena, Schenke, Lea, Klose, Diana, Amoury, Manal, Woitok, Mira, Jost, Edgar, Brümmendorf, Tim H., Fendel, Rolf, Fischer, Rainer, Stein, Christoph, Thepen, Theo, Barth, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341865/
https://www.ncbi.nlm.nih.gov/pubmed/27564103
http://dx.doi.org/10.18632/oncotarget.11568
Descripción
Sumario: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.