Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation

Perry Maxwell, Florinda Melendez-Rodriguez, Kyle B Matchett, Julian Aragones, Nathalie Ben-Califa, Heidelinde Jaekel, Ludger Hengst, Herbert Lindner, Andre Bernardini, Ulf Brockmeier, Joachim Fandrey, Fritz Grunert, Howard S Oster, Moshe Mittelman, Mohamed El-Tanani, Markus Thiersch, Edith M Scheider Gasser, Max Gassmann, David Dangoor, Robert J Cuthbert & 5 others Alexandra Irvine, Anne Jordan, Terence Lappin, John Thompson, Drorit Neumann

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.
LanguageEnglish
Pages429-442
Number of pages14
JournalBritish Journal of Haematology
Volume168
Issue number3
Publication statusPublished - 1 Feb 2015

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Erythropoietin Receptors
Erythropoietin
Antibodies
Neoplasms
Patient Participation
Cell Line
Immunoprecipitation
Fluorescent Antibody Technique
Disease Progression
Anemia
Immunization
Flow Cytometry
Protein Isoforms
Western Blotting
Immunohistochemistry
Monoclonal Antibodies
Messenger RNA
Peptides
Therapeutics
Research

Cite this

Maxwell, P., Melendez-Rodriguez, F., Matchett, K. B., Aragones, J., Ben-Califa, N., Jaekel, H., ... Neumann, D. (2015). Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation. British Journal of Haematology, 168(3), 429-442.
Maxwell, Perry ; Melendez-Rodriguez, Florinda ; Matchett, Kyle B ; Aragones, Julian ; Ben-Califa, Nathalie ; Jaekel, Heidelinde ; Hengst, Ludger ; Lindner, Herbert ; Bernardini, Andre ; Brockmeier, Ulf ; Fandrey, Joachim ; Grunert, Fritz ; Oster, Howard S ; Mittelman, Moshe ; El-Tanani, Mohamed ; Thiersch, Markus ; Scheider Gasser, Edith M ; Gassmann, Max ; Dangoor, David ; Cuthbert, Robert J ; Irvine, Alexandra ; Jordan, Anne ; Lappin, Terence ; Thompson, John ; Neumann, Drorit. / Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation. In: British Journal of Haematology. 2015 ; Vol. 168, No. 3. pp. 429-442.
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Maxwell, P, Melendez-Rodriguez, F, Matchett, KB, Aragones, J, Ben-Califa, N, Jaekel, H, Hengst, L, Lindner, H, Bernardini, A, Brockmeier, U, Fandrey, J, Grunert, F, Oster, HS, Mittelman, M, El-Tanani, M, Thiersch, M, Scheider Gasser, EM, Gassmann, M, Dangoor, D, Cuthbert, RJ, Irvine, A, Jordan, A, Lappin, T, Thompson, J & Neumann, D 2015, 'Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation', British Journal of Haematology, vol. 168, no. 3, pp. 429-442.

Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation. / Maxwell, Perry; Melendez-Rodriguez, Florinda; Matchett, Kyle B; Aragones, Julian; Ben-Califa, Nathalie; Jaekel, Heidelinde; Hengst, Ludger; Lindner, Herbert; Bernardini, Andre; Brockmeier, Ulf; Fandrey, Joachim; Grunert, Fritz; Oster, Howard S; Mittelman, Moshe; El-Tanani, Mohamed; Thiersch, Markus; Scheider Gasser, Edith M; Gassmann, Max; Dangoor, David; Cuthbert, Robert J; Irvine, Alexandra; Jordan, Anne; Lappin, Terence; Thompson, John; Neumann, Drorit.

In: British Journal of Haematology, Vol. 168, No. 3, 01.02.2015, p. 429-442.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation

AU - Maxwell, Perry

AU - Melendez-Rodriguez, Florinda

AU - Matchett, Kyle B

AU - Aragones, Julian

AU - Ben-Califa, Nathalie

AU - Jaekel, Heidelinde

AU - Hengst, Ludger

AU - Lindner, Herbert

AU - Bernardini, Andre

AU - Brockmeier, Ulf

AU - Fandrey, Joachim

AU - Grunert, Fritz

AU - Oster, Howard S

AU - Mittelman, Moshe

AU - El-Tanani, Mohamed

AU - Thiersch, Markus

AU - Scheider Gasser, Edith M

AU - Gassmann, Max

AU - Dangoor, David

AU - Cuthbert, Robert J

AU - Irvine, Alexandra

AU - Jordan, Anne

AU - Lappin, Terence

AU - Thompson, John

AU - Neumann, Drorit

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

M3 - Article

VL - 168

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EP - 442

JO - British Journal of Haematology

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JF - British Journal of Haematology

SN - 0007-1048

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Maxwell P, Melendez-Rodriguez F, Matchett KB, Aragones J, Ben-Califa N, Jaekel H et al. Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation. British Journal of Haematology. 2015 Feb 1;168(3):429-442.