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Macrophage-Targeted Therapy: CD64-Based Immunotoxins for Treatment of Chronic Inflammatory Diseases
Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital RWTH Aachen, Aachen 52074, Germany
Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology, Aachen 52074, Germany
* Author to whom correspondence should be addressed.
Received: 16 August 2012; in revised form: 4 September 2012 / Accepted: 5 September 2012 / Published: 14 September 2012
Abstract: Diseases caused by chronic inflammation (e.g., arthritis, multiple sclerosis and diabetic ulcers) are multicausal, thus making treatment difficult and inefficient. Due to the age-associated nature of most of these disorders and the demographic transition towards an overall older population, efficient therapeutic intervention strategies will need to be developed in the near future. Over the past decades, elimination of activated macrophages using CD64-targeting immunotoxins has proven to be a promising way of resolving inflammation in animal models. More recent data have shown that the M1-polarized population of activated macrophages in particular is critically involved in the chronic phase. We recapitulate the latest progress in the development of IT. These have advanced from full-length antibodies, chemically coupled to bacterial toxins, into single chain variants of antibodies, genetically fused with fully human enzymes. These improvements have increased the range of possible target diseases, which now include chronic inflammatory diseases. At present there are no therapeutic strategies focusing on macrophages to treat chronic disorders. In this review, we focus on the role of different polarized macrophages and the potential of CD64-based IT to intervene in the process of chronic inflammation.
Keywords: CD64; macrophages; polarization; immunotoxins; inflammation
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Hristodorov, D.; Mladenov, R.; Huhn, M.; Barth, S.; Thepen, T. Macrophage-Targeted Therapy: CD64-Based Immunotoxins for Treatment of Chronic Inflammatory Diseases. Toxins 2012, 4, 676-694.
Hristodorov D, Mladenov R, Huhn M, Barth S, Thepen T. Macrophage-Targeted Therapy: CD64-Based Immunotoxins for Treatment of Chronic Inflammatory Diseases. Toxins. 2012; 4(9):676-694.
Hristodorov, Dmitrij; Mladenov, Radoslav; Huhn, Michael; Barth, Stefan; Thepen, Theo. 2012. "Macrophage-Targeted Therapy: CD64-Based Immunotoxins for Treatment of Chronic Inflammatory Diseases." Toxins 4, no. 9: 676-694.