THE rhGM-CSF–EPO HYBRID PROTEIN MEN 11300 INDUCES ANTI-EPO ANTIBODIES AND SEVERE ANAEMIA IN RHESUS MONKEYS

Coscarella, Annamaria; Liddi, Roberto; Loreto, Mario Di; Bach, Simona; Faiella, Angela; Meide, P. H. Van Der; Mele, Antonio; Santis, Rita De

doi:10.1006/cyto.1998.0384

Cited by 21 publications

(9 citation statements)

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“…Another dimeric fusion protein incorporating both EPO and granulocyte macrophage colonystimulating factor (GM-CSF) has been created, with the rationale that GM-CSF is required for early erythropoiesis. This EPO-GM-CSF complex proved to be able to stimulate erythropoiesis in cynomolgus monkeys (28) but was later found to induce anti-EPO antibodies, causing severe anemia (29). Yet another approach is the genetic fusion of EPO with the Fc region of human IgG (Fc-EPO) (30).…”

Section: Other Protein-based Epo Derivativesmentioning

confidence: 99%

Novel Erythropoiesis-Stimulating Agents

Macdougall

2008

Clinical Journal of the American Society of Nephrology

102

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Nearly two decades ago, recombinant human erythropoietin transformed the management of chronic kidney disease anemia by allowing a more sustained increase in hemoglobin than was possible by intermittent blood transfusion. The treatment was highly effective, but because of the fairly short half-life of the molecule at approximately 6 to 8 h, injections usually had to be administered two to three times weekly. A second-generation erythropoietin analogue, darbepoetin alfa, was then created, with a longer elimination half-life in vivo that translated into less frequent dosing, usually once weekly or once every 2 wk. More recently, another erythropoietin-related molecule has been produced called Continuous Erythropoietin Receptor Activator with an even greater half-life, and other molecules are in development or are being licensed, including biosimilar epoetin products and Hematide. The latter is a synthetic peptide-based erythropoietin receptor agonist that, interestingly, has no structural homology with erythropoietin, and yet is still able to activate the erythropoietin receptor and stimulate erythropoiesis. The search goes on for orally active antianemic therapies, and several strategies are being investigated, although none is imminently available. This article reviews the latest progress with these novel erythropoietic agents in this new era in anemia management.

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Section: Other Protein-based Epo Derivativesmentioning

confidence: 99%

Novel Erythropoiesis-Stimulating Agents

Macdougall

2008

Clinical Journal of the American Society of Nephrology

102

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“…Another dimeric fusion protein incorporating both EPO and GM-CSF has been created, with the rationale that GM-CSF is required for early erythropoiesis. This EPO-GM-CSF complex proved to be able to stimulate erythropoiesis in cynomolgus monkeys (Coscarella et al, 1998a), but was later found to induce anti-erythropoietin antibodies, causing severe anemia (Coscarella et al, 1998b). Yet another approach is the genetic fusion of EPO with the Fc region of human immunoglobulin G (Fc-EPO) (Way et al, 2005).…”

Section: Potential Strategies For Modifying Erythropoietin To Crementioning

confidence: 99%

Development of Recombinant Erythropoietin and Erythropoietin Analogs

Macdougall

2009

Textbook of Nephro-Endocrinology

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“…Unfortunately, that molecule was later found to induce anti-Epo antibodies and severe anaemia as well [24] .…”

Section: Fusion Peptidesmentioning

confidence: 99%

Stimulating Erythropoiesis: Future Perspectives

Mikhail

Covic

Goldsmith

2008

Kidney Blood Press Res

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The introduction of recombinant human erythropoietin (rHuEpo) nearly 20 years ago has revolutionised the management of patients with CKD, providing the opportunity for safe long-term anaemia correction without the attendant risks identified with blood products. Based on our expanding knowledge in this area, there are many exciting and innovative new approaches to anaemia correction that stand on, or are close to, the threshold of yielding products ready for clinical use. Recently, an Epo-related molecule called continuous Epo receptor activator has been licensed in Europe, and other molecules are in various processes of development, including Epo mimetic peptide. The search goes on for orally active antianaemic therapies, and several strategies are being investigated. Furthermore, it is now clear that in addition to the anaemia-correction properties of erythropoiesis-stimulating agents, there is the potential for cytoprotection by prevention of cellular apoptosis. This effect could be used in the prevention of ischaemia-reperfusion injury as well as other conditions associated with acute kidney injury and other disease processes. The aim of this article is to discuss these possible future strategies, focusing in particular on those with a reasonable likelihood of a pharmaceutical product that is likely to be used clinically.

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THE rhGM-CSF–EPO HYBRID PROTEIN MEN 11300 INDUCES ANTI-EPO ANTIBODIES AND SEVERE ANAEMIA IN RHESUS MONKEYS

Cited by 21 publications

References 0 publications

Novel Erythropoiesis-Stimulating Agents

Novel Erythropoiesis-Stimulating Agents

Development of Recombinant Erythropoietin and Erythropoietin Analogs

Stimulating Erythropoiesis: Future Perspectives

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