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Biochemistry (Moscow)

, Volume 81, Issue 11, pp 1396–1400 | Cite as

Immunogenicity of human interferon-beta-containing pharmaceuticals

  • V. D. NazarovEmail author
  • S. V. Lapin
  • A. V. Mazing
  • E. P. Evdoshenko
  • A. A. Totolian
Molecular and Cellular Mechanisms of Inflammation (Special Issue) Guest Editors S. A. Nedospasov and D. V. Kuprash

Abstract

Multiple sclerosis is a severe autoimmune disease with inflammatory component that continues to be resistant to treatment. One of the approaches retarding its progression is based on using nonspecific therapy with human interferon-beta (IFN-β)-containing pharmaceuticals. Neutralizing antibodies (NAbs) against genetically engineered pharmaceuticals developed by the patient’s immune system, which reduce their therapeutic and biological activity, pose a serious problem. Cell lines sensitive to IFN-β activity also quantifying NAb level are applied because direct measurement of IFN-β antiviral activity is complicated. This study was aimed at standardization and validation of a reporter cell system for measuring antihuman IFN-β NAb titers, and evaluation data were obtained with samples from 33 patients with multiple sclerosis.

Keywords

multiple sclerosis immunogenicity interferon-beta neutralizing antibodies titer 

Abbreviations

BTPs

biotherapeutic products

IFN-β

interferon-beta

LU

laboratory unit

MS

multiple sclerosis

NAbs

neutralizing antibodies

RF

rheumatoid factor

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References

  1. 1.
    Rader, R. (2008) Redefining biopharmaceutical, Nat. Biotechnol., 26, 743–751.CrossRefPubMedGoogle Scholar
  2. 2.
    Baumann, A. (2006) Early development of therapeutic biologics–pharmacokinetics, Curr. Drug Metab., 7, 15–21.CrossRefPubMedGoogle Scholar
  3. 3.
    Wadhwa, M., Knezevic, I., Kang, H. N., and Thorpe, R. (2015) Immunogenicity assessment of biotherapeutic products: an overview of assays and their utility, Biologicals, 43, 298–306.CrossRefPubMedGoogle Scholar
  4. 4.
    WHO. Guidelines on clinical evaluation of vaccines: regulatory expectations (2004) WHO Tech Rep., 924, 35–102.Google Scholar
  5. 5.
    Van Beers, M. M. C., and Bardor, M. (2012) Minimizing immunogenicity of biopharmaceuticals by controlling critical quality attributes of proteins, Biotechnol. J., 7, 14731484.Google Scholar
  6. 6.
    Nazarov, V. D., Lapin, S. V., Surkova, E. A., Evdoshenko, E. P., Makshakov, G. S., and Totolian, A. A. (2015) Diagnostic and prognostic significance of intrathecal synthesis of immunoglobulin free light chains in multiple sclerosis, Med. Immunol. (Moscow), 17, 235–244.CrossRefGoogle Scholar
  7. 7.
    Nikfar, S., Rahimi, R., and Abdollahi, M. (2010) A metaanalysis of the efficacy and tolerability of interferon-ß in multiple sclerosis, overall and by drug and disease type, Clin. Ther., 32, 1871–1888.PubMedGoogle Scholar
  8. 8.
    Govindappa, K., Sathish, J., Park, K., Kirkham, J., and Pirmohamed, M. (2015) Development of interferon betaneutralizing antibodies in multiple sclerosis–a systematic review and meta-analysis, Eur. J. Clin. Pharmacol., 71, 1287–1298.CrossRefPubMedGoogle Scholar
  9. 9.
    Van Beers, M. M., Jiskoot, W., and Schellekens, H. (2010) On the role of aggregates in the immunogenicity of recombinant human interferon beta in patients with multiple sclerosis, J. Interf. Cytokine Res., 30, 767–775.CrossRefGoogle Scholar
  10. 10.
    Polman, C. H., Bertolotto, A., Deisenhammer, F., Giovannoni, G., Hartung, H. P., Hemmer, B., Killestein, J., McFarland, H. F., Oger, J., Pachner, A. R., Petkau, J., Reder, A. T., Reingold, S. C., Schellekens, H., and Sorensen, P. S. (2010) Recommendations for clinical use of data on neutralizing antibodies to interferon-beta therapy in multiple sclerosis, Lancet Neurol., 9, 740–750.CrossRefPubMedGoogle Scholar
  11. 11.
    WHO Expert Committee on Biological Standardization. Thirty-fifth report (1985) World Health Organ. Tech. Rep. Ser., 725, 1–140.Google Scholar
  12. 12.
    Deisenhammer, F. (2014) Interferon-beta: neutralizing antibodies, binding antibodies, pharmacokinetics and pharmacodynamics, and clinical outcomes, J. Interferon Cytokine Res., 34, 938–945.Google Scholar
  13. 13.
    Lam, R., Farrell, R., Aziz, T., Gibbs, E., Giovannoni, G., Großsberg, S., and Oger, J. (2008) Validating parameters of a luciferase reporter gene assay to measure neutralizing antibodies to IFNß in multiple sclerosis patients, J. Immunol. Methods, 336, 113–118.CrossRefPubMedGoogle Scholar
  14. 14.
    Kawade, Y., Finter, N., and Grossberg, S. E. (2003) Neutralization of the biological activity of cytokines and other protein effectors by antibody: theoretical formulation of antibody titration curves in relation to antibody affinity, J. Immunol. Methods, 278, 127–144.CrossRefPubMedGoogle Scholar
  15. 15.
    Meager, A., Dolman, C., Dilger, P., Bird, C., Giovannoni, G., Schellekens, H., Thorpe, R., and Wadhwa, M. (2011) An assessment of biological potency and molecular characteristics of different innovator and noninnovator interferon-beta products, J. Interferon Cytokine Res., 31, 383–392.CrossRefPubMedGoogle Scholar
  16. 16.
    Gneiss, C., Tripp, P., Reichartseder, F., Egg, R., Ehling, R., Lutterotti, A., Khalil, M., Kuenz, B., Mayringer, I., Reindl, M., Berger, T., and Deisenhammer, F. (2006) Differing immunogenic potentials of interferon beta preparations in multiple sclerosis patients, Mult. Scler., 12, 731–737.CrossRefPubMedGoogle Scholar
  17. 17.
    Roßs, C., Clemmesen, K. M., Sorensen, P. S., KochHenriksen, N., and Bendtzen, K. (2006) Measuring and evaluating interferon ß-induced antibodies in patients with multiple sclerosis, Mult. Scler., 12, 39–46.CrossRefGoogle Scholar
  18. 18.
    Manfredonia, F., Pasquali, L., Dardano, A., Iudice, A., Murri, L., and Monzani, F. (2008) Review of the clinical evidence for interferon ß 1a (Rebif) in the treatment of multiple sclerosis, Neuropsychiatr. Dis. Treat., 4, 321–336.PubMedPubMedCentralGoogle Scholar
  19. 19.
    The IFNB Multiple Sclerosis Study Group (1993) Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial, Neurology, 43, 655–661.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  • V. D. Nazarov
    • 1
    Email author
  • S. V. Lapin
    • 1
  • A. V. Mazing
    • 1
  • E. P. Evdoshenko
    • 2
  • A. A. Totolian
    • 1
    • 3
  1. 1.Center for Molecular MedicinePavlov First Saint Petersburg State Medical UniversitySt. PetersburgRussia
  2. 2.Saint-Petersburg Center of Multiple Sclerosis and Autoimmune Diseases Clinical Hospital No. 31St. PetersburgRussia
  3. 3.Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology (St. Petersburg Pasteur Institute)St. PetersburgRussia

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