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  • Title: Molecular evidence of transient therapeutic effectiveness of natalizumab despite high-titre neutralizing antibodies.
    Author: Pilz G, Harrer A, Oppermann K, Wipfler P, Golaszewski S, Afazel S, Haschke-Becher E, Trinka E, Kraus J.
    Journal: Mult Scler; 2012 Apr; 18(4):506-9. PubMed ID: 21965415.
    Abstract:
    Natalizumab is a humanized monoclonal antibody directed against the alpha-4 integrin subunit of very late activation antigen-4 (VLA-4). Natalizumab neutralizing antibodies (NAB) have been found to significantly reduce beneficial effects of natalizumab treatment in multiple sclerosis. We investigated interactions of NAB with natalizumab by serial measurements of alpha-4 integrin levels on peripheral blood mononuclear cells using flow cytometry. In addition, serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), the endothelial ligand of VLA-4, and serum NAB were serially determined. Natalizumab infusion led to a transient reduction in alpha-4 integrin levels on immune cells and serum sVCAM-1 levels along with serum negativity of NAB lasting for a few days post-infusion. Apparently, the high-dose effect of freshly infused natalizumab resulted in a transient neutralization of NAB possibly involving a transient therapeutic effectiveness.
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