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

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.

• Authors: 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, Stefan Barth
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 41 Pg. 67166-67174 (Oct 11 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27564103 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• FCGR1A protein, human
• Immunotoxins
• Microtubule-Associated Proteins
• Receptors, IgG
• Recombinant Fusion Proteins

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (pharmacology)
• Cells, Cultured
• Female
• Humans
• Immunotoxins (pharmacology)
• Leukemia, Myeloid, Acute
• Male
• Microtubule-Associated Proteins (pharmacology)
• Middle Aged
• Molecular Targeted Therapy (methods)
• Receptors, IgG
• Recombinant Fusion Proteins (pharmacology)