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Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation
Author(s) -
Maxwell Perry,
MelendezRodríguez Florinda,
Matchett Kyle B.,
Aragones Julian,
BenCalifa Nathalie,
Jaekel Heidelinde,
Hengst Ludger,
Lindner Herbert,
Bernardini Andre,
Brockmeier Ulf,
Fandrey Joachim,
Grunert Fritz,
Oster Howard S.,
Mittelman Moshe,
ElTanani Mohamed,
Thiersch Markus,
Schneider Gasser Edith M.,
Gassmann Max,
Dangoor David,
Cuthbert Robert J.,
Irvine Alexandra,
Jordan Anne,
Lappin Terence,
Thompson John,
Neumann Drorit
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13133
Subject(s) - erythropoietin receptor , antibody , erythropoietin , monoclonal antibody , biology , cancer research , western blot , immunohistochemistry , polyclonal antibodies , medicine , immunology , endocrinology , gene , genetics
Summary Recombinant human erythropoietin (r H u EPO ) 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 m RNA level but investigations of these variants and their potential impact on tumour progression, have been hampered by lack of suitable antibodies. The E po C an consortium seeks to promote improved pathological testing of EPOR , leading to safer clinical use of r H u EPO , 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 W estern 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 r H u EPO from those at increased risk from treatment.