Yes / 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 contro- versial 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 sev- eral of these specifically recognize EPOR by Western blot, immunoprecipi- tation, 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. / Study was supported by the FP7-Health European commission EpoCan grant (282551).
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/8404 |
| Date | 04 October 2015 |
| Creators | Maxwell, P., Melendez-Rodriguez, F., Matchett, K.B., Aragones, J., Ben-Califa, N., Jackel, H., Hengst, L., Lindner, H., Bernardini, A., Brockmeier, U., Fandrey, J., Grunert, F., Oster, H.S., Mittelman, M., El-Tanani, Mohamed, Thiersch, M., Schneider Gasser, E.M., Gassmann, M., Dangoor, D., Cuthbert, R.J., Irvine, A., Jordan, A., Lappin, T.R., Thompson, J., Neumann, D. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted Manuscript |
| Rights | © 2014 Wiley This is the peer reviewed version of the following article: Maxwell P, Melendez-Rodriguez F, Matchett KB et al. (2015) Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation. British Journal of Haematology. 168: 429-442, which has been published in final form at http://dx.doi.org/10.1111/bjh.13133 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
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