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. 2016 May;94(5):470-8.
doi: 10.1038/icb.2016.4. Epub 2016 Jan 8.

Fully human MAP-fusion protein selectively targets and eliminates proliferating CD64(+) M1 macrophages

Dmitrij Hristodorov  1 , Radoslav Mladenov  1 , Rainer Fischer  2   3 , Stefan Barth  1   2 , Theo Thepen  2
Affiliations

Fully human MAP-fusion protein selectively targets and eliminates proliferating CD64(+) M1 macrophages

Dmitrij Hristodorov et al. Immunol Cell Biol. 2016 May.

Abstract

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.

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References

    1. Am J Gastroenterol. 2009 Jan;104(1):102-9 - PubMed
    1. Arthritis Res Ther. 2009;11(1):R6 - PubMed
    1. J Immunother. 2008 May;31(4):370-6 - PubMed
    1. Cancer Sci. 2009 Aug;100(8):1359-65 - PubMed
    1. Cancer Lett. 2015 Sep 1;365(2):149-55 - PubMed

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