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Fully human MAP‐fusion protein selectively targets and eliminates proliferating CD64 + M1 macrophages
Author(s) -
Hristodorov Dmitrij,
Mladenov Radoslav,
Fischer Rainer,
Barth Stefan,
Thepen Theo
Publication year - 2016
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2016.4
Subject(s) - immunotoxin , fusion protein , biology , inflammation , pseudomonas exotoxin , in vitro , immunology , cancer research , antibody , cytotoxicity , monoclonal antibody , recombinant dna , biochemistry , gene
Classical immunotoxins compromise a binding component (for example, a ligand, antibody or fragment thereof) and a cytotoxic component, usually derived from bacteria or plants (for example, Pseudomonas exotoxin A or ricin). Despite successful testing in vitro , the clinical development of immunotoxins has been hampered by immunogenicity and unsatisfactory safety profiles. Therefore, research has focused on fully human pro‐apoptotic components suitable for the development of cytolytic fusion proteins (CFP). We recently reported that human microtubule‐associated protein tau (MAP) can induce apoptosis when delivered to rapidly proliferating cancer cells. Here, we describe a new fully human CFP called H22(scFv)‐MAP, which specifically targets CD64 + cells. We show that H22(scFv)‐MAP can efficiently kill proliferating HL‐60 pro‐monocytic cells in vitro. In addition, the human CFP specifically eliminates polarized M1 macrophages in a transgenic mouse model of cutaneous chronic inflammation. Because M1 macrophages promote the pathogenesis of many chronic inflammatory diseases, targeting this cell population with H22(scFv)‐MAP could help to treat diseases such as atopic dermatitis, rheumatoid arthritis and inflammatory bowel disease.