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Macrophage-targeted therapy: CD64-based immunotoxins for treatment of chronic inflammatory diseases.

Hristodorov D, Mladenov R, Huhn M, Barth S, Thepen T - Toxins (Basel) (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital RWTH Aachen, Aachen 52074, Germany. dmitrij.hristodorov@rwth-aachen.de

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.

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Related in: MedlinePlus

Basic architecture of Immunotoxins (IT).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3475223&req=5

toxins-04-00676-f001: Basic architecture of Immunotoxins (IT).

Mentions: Immunotoxins (IT) are chimeric proteins consisting of a binding domain, which is commonly an antibody or a derivative thereof, and a toxic domain, which is an enzyme usually derived from bacteria or plants (Figure 1). Abbreviations: Ag, antigen; Ab, antibody; Fab, fragment antigen binding; scFv: single chain fragment variable.


Macrophage-targeted therapy: CD64-based immunotoxins for treatment of chronic inflammatory diseases.

Hristodorov D, Mladenov R, Huhn M, Barth S, Thepen T - Toxins (Basel) (2012)

Basic architecture of Immunotoxins (IT).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475223&req=5

toxins-04-00676-f001: Basic architecture of Immunotoxins (IT).
Mentions: Immunotoxins (IT) are chimeric proteins consisting of a binding domain, which is commonly an antibody or a derivative thereof, and a toxic domain, which is an enzyme usually derived from bacteria or plants (Figure 1). Abbreviations: Ag, antigen; Ab, antibody; Fab, fragment antigen binding; scFv: single chain fragment variable.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital RWTH Aachen, Aachen 52074, Germany. dmitrij.hristodorov@rwth-aachen.de

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.

Show MeSH
Related in: MedlinePlus