Assessment of Unwanted Immunogenicity

  • Meenu Wadhwa
  • Robin Thorpe
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume VIII)


Therapeutic Protein Sensor Chip Antibody Assay Neutralization Assay Potency Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baert, F., Noman, M., Vermiere, S., Assche, G. V., D’Haens, G., Carbonez, A., and Rutgeerts, P. 2003. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N. Engl. J. Med. 348:601–608.PubMedCrossRefGoogle Scholar
  2. Bertolotto, A. 2004. Neutralizing antibodies to interferon beta: implications for the management of multiple sclerosis. Curr. Opin. Neurol. 17:241–246.PubMedCrossRefGoogle Scholar
  3. Brickelmaier, M., Hochman, P. S., Baciu, R., Chao, B., Cuervo, J. H., and Whitty, A. 1999. ELISA methods for the analysis of antibody responses induced in multiple sclerosis patients treated with recombinant interferon-beta. J. Immunol. Meth. 227:121–135.CrossRefGoogle Scholar
  4. Casadevall, N., Nataf, J., Viron, B., Kolta, A., Kiladjian, J. J., Martin-Dupont, P., Michaud, P., Papo, T., Ugo, V., Teyssandier, I., Varet, B., and Mayeux, P. 2002. Pure red cell aplasia and anti-erythropoietin antibodies against human erythropoietin in patients treated with recombinant erythropoietin. N. Engl. J. Med. 346:469–475.PubMedCrossRefGoogle Scholar
  5. CHMP (Committee for medicinal products for human use). 2007. Guideline on Immunogenicity assessment of biotechnology-derived therapeutic proteins. EMEA/CHMP/BMWP/14327/2006 – draft version released for consultation.Google Scholar
  6. Gross, J., Moller, R., Henke, W., and Hoesel, W. 2006. Detection of anti-EPO antibodies in human sera by a bridging ELISA is much more sensitive when coating biotinylated rhEPO to streptavidin rather than using direct coating of rhEPO. J. Immunol. Meth. 313:176–182.CrossRefGoogle Scholar
  7. Gupta, S., Indelicato, S. R., Jethwa, V., Kawabata, T., Marian Kelley, M., Mire-Sluis, A. R., Richards, S. M., Rup, B., Shores, E., Swanson, S. J., and Wakshull E. 2007. Recommendations for the design, optimization, and qualification of cell-based assays used for the detection of neutralizing antibody responses elicited to biological therapeutics. J. Immunol. Meth. 321:1–18.CrossRefGoogle Scholar
  8. Hemmer, B., Stuve, O., Kieseier, B., Schellekens, H., and Hartung, H. P. 2005. Immune response to immunotherapy: the role of neutralising antibodies to interferon beta in the treatment of multiple sclerosis. Lancet Neurol. 4:403–412.PubMedCrossRefGoogle Scholar
  9. International Conference on Harmonization. 1997. Guidance for Industry. S6 Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals. Available at ( Scholar
  10. Koren, E., Zuckerman, L. A., and Mire-Sluis, A. R. 2002. Immune responses to therapeutic proteins in humans – clinical significance, assessment and prediction. Curr. Pharm. Biotechnol. 3:349–360.PubMedCrossRefGoogle Scholar
  11. Li, J., Yang, C., Xia, Y., Bertino, A., Glaspy, J., Roberts, M., and Kuter, D. J. 2001. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 98:3241–3248.PubMedCrossRefGoogle Scholar
  12. Lofgren, J. A., Wala, I., Koren, E., Swanson, S. J., and Jing, S. 2006. Detection of neutralizing anti-therapeutic protein antibodies in serum or plasma samples containing high levels of the therapeutic protein. J. Immunol. Meth. 308:101–108.CrossRefGoogle Scholar
  13. Menetrier-Caux, C., Briere, F., Jouvenne, P., Peyron, E., Peyron, F., Banchereau, J. 1996. Identification of human IgG autoantibodies specific for IL-10. Clin. Exp. Immunol. 104:173–179.PubMedCrossRefGoogle Scholar
  14. McKay, F., Schibeci, S., Heard, R., Stewart, G., and Booth, D. 2005. Analysis of neutralizing antibodies to therapeutic interferon-beta in multiple sclerosis patients: A comparison of three methods in a large Australasian cohort. J. Immunol. Meth. 310:20–29.CrossRefGoogle Scholar
  15. Mire-Sluis, A. R., Barrett, Y. C., Devanarayan, V., Koren E., Liu, H., Maia, M., Parish, T., Scott, G., Shankar, G., Shores, E., Swanson, S. J., Taniguchi, G., Wierda, D., and Zuckerman, L. A. 2004. Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J. Immunol. Meth. 289:1–16.CrossRefGoogle Scholar
  16. Patton, A., Mullenix, M. C., Swanson, S. J., Koren, E. 2005. An acid dissociation bridging ELISA for detection of antibodies directed against therapeutic proteins in the presence of antigen. J. Immunol. Meth. 304:189–195.CrossRefGoogle Scholar
  17. Swanson, S. J. 2005. Characterization of an immune response. Dev. Biol. 122:95–101.Google Scholar
  18. Tacey, R., Greway, A., Smiell, J., Power, D., Kromminga, A., Daha, M., Casadevall, N., and Kelley, M. 2003. The detection of anti-erythropoietin antibodies in human serum and plasma: Part I. Validation of the protocol for a radioimmunoprecipitation assay. J. Immunol. Meth. 283:317–329.CrossRefGoogle Scholar
  19. Thorpe, R., and Swanson, S. J. 2005. Current methods for detecting antibodies against Erythropoietin and other recombinant proteins. Clin. Diag. Lab. Immunol. 12:28–39.CrossRefGoogle Scholar
  20. Ullenhag, G., Bird, C., Ragnhammar, P., Frodin, J. E., Strigard, K., Osterborg, A., Thorpe, R. Mellstedt, H., and Wadhwa, M. 2001. Incidence of GM-CSF antibodies in cancer patients receiving low dose GM-CSF as an adjuvant. Clin. Immunol. 99:65–74.PubMedCrossRefGoogle Scholar
  21. Wadhwa, M., Bird, C., Fagerberg, J., Gaines-Das, R., Ragnhammar, P., Mellstedt, H., and Thorpe, R. 1996. Production of neutralizing GM-CSF antibodies in carcinoma patients following GM-CSF combination therapy. Clin. Exp. Immunol. 104:351–358.PubMedCrossRefGoogle Scholar
  22. Wadhwa, M., Skog, A.-L. H., Bird, C., Ragnhammar, P., Lilljefors, M., Gaines-Das, R., Mellstedt, H., and Thorpe, R. 1999. Immunogenicity of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) products in patients undergoing combination therapy with GM-CSF. Clin. Can. Res. 5:1353–1361.Google Scholar
  23. Wadhwa, M., Bird, C., Dilger, P., Gaines-Das, R., and Thorpe, R. 2003. Strategies for detection, measurement and characterization of unwanted antibodies induced by therapeutic biologicals. J. Immunol. Meth. 278:1–17.CrossRefGoogle Scholar
  24. Wadhwa, M., and Thorpe, R. 2006 Strategies and assays for the assessment of unwanted immunogenic. J. Immunotoxicology 3:115–121.CrossRefGoogle Scholar
  25. Wei, X., Swanson, S. J., and Gupta, S. 2004. Development and validation of a cell-based bioassay for the detection of neutralizing antibodies against recombinant human erythropoietin in clinical studies. J. Immunol. Meth. 293:115–126.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  • Meenu Wadhwa
  • Robin Thorpe

There are no affiliations available

Personalised recommendations