Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation.
Br J Haematol
; 168(3): 429-42, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25283956
ABSTRACT
Recombinant human erythropoietin (rHuEPO) is an effective treatment for anaemia but concerns that it causes disease progression in cancer patients by activation of EPO receptors (EPOR) in tumour tissue have been controversial and have restricted its clinical use. Initial clinical studies were flawed because they used polyclonal antibodies, later shown to lack specificity for EPOR. Moreover, multiple isoforms of EPOR caused by differential splicing have been reported in cancer cell lines at the mRNA level but investigations of these variants and their potential impact on tumour progression, have been hampered by lack of suitable antibodies. The EpoCan consortium seeks to promote improved pathological testing of EPOR, leading to safer clinical use of rHuEPO, by producing well characterized EPOR antibodies. Using novel genetic and traditional peptide immunization protocols, we have produced mouse and rat monoclonal antibodies, and show that several of these specifically recognize EPOR by Western blot, immunoprecipitation, immunofluorescence, flow cytometry and immunohistochemistry in cell lines and clinical material. Widespread availability of these antibodies should enable the research community to gain a better understanding of the role of EPOR in cancer, and eventually to distinguish patients who can be treated safely by rHuEPO from those at increased risk from treatment.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores da Eritropoetina
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Anticorpos Monoclonais
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Proteínas de Neoplasias
Tipo de estudo:
Etiology_studies
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Guideline
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido