Identification of fibrinogen as a plasma protein binding partner for lecanemab biosimilar IgG.

Autor: Bellier JP; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Román Viera AM; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Christiano C; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Anzai JAU; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Moreno S; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Campbell EC; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Godwin L; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Li A; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Chen AY; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Alam SM; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Saba A; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Yoo HB; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Yang HS; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Chhatwal JP; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Selkoe DJ; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Liu L; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2024 Oct 30. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1002/acn3.52227
Abstrakt: Objective: Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer's disease, offer a promising approach for modifying the disease progression. Due to its relatively short half-life, lecanemab administered as a bi-monthly infusion (typically 10 mg/kg) has a relatively brief half-life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half-life. In this study, we investigated potential plasma protein binding (PPB) interaction to lecanemab using lecanemab biosimilar.
Methods: Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions of human plasma obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate plasma binders was confirmed by western blotting, ELISA, and surface plasmon resonance analysis.
Results: Using a combination of equilibrium dialysis, ELISA, and western blotting in human plasma, we first describe the presence of likely PPB partners to lecanemab biosimilar and then identify fibrinogen as one of them. Utilizing surface plasmon resonance, we confirmed that lecanemab biosimilar does bind to fibrinogen, although with lower affinity than to monomeric amyloid beta.
Interpretation: In the context of lecanemab therapy, these results imply that fibrinogen levels could impact the levels of free antibodies in the bloodstream and that fibrinogen might serve as a reservoir for lecanemab. More broadly, these results indicate that PPB may be an important consideration when clinically utilizing therapeutic antibodies in neurodegenerative disease.
(© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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