On the role of aggregates in the immunogenicity of recombinant human interferon beta in patients with multiple sclerosis.
Like many other therapeutic proteins, recombinant human interferon beta (rhIFN-&#x03B2;) elicits undesirable immune responses. rhIFN-&#x03B2;-treated multiple sclerosis patients may form binding antibodies and neutralizing antibodies (NAbs), with the latter being responsible for inhibition of the therapeutic effect of the protein. The incidence of binding antibodies and NAbs against rhIFN-&#x03B2; as well as the titer and persistence of NAbs differ among the marketed products. The proportion of patients forming antibodies against rhIFN-&#x03B2;-1b is higher than that against rhIFN-&#x03B2;-1a, which is likely explained by the differences in protein structure and aggregation behavior between the 2 types of rhIFN-&#x03B2;. Here, we summarize the different factors influencing the immunogenicity of rhIFN-&#x03B2; in patients with multiple sclerosis and discuss the role played by rhIFN-&#x03B2; aggregates.
van Beers
Miranda M C
MM
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
Jiskoot
Wim
W
Schellekens
Huub
H
D000906:Antibodies / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000937:Antigen-Antibody Reactions; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use
D000906:Antibodies; D057134:Antibodies, Neutralizing; D011994:Recombinant Proteins; D016899:Interferon-beta