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Peptide Mimotope-Enabled Quantification of Natalizumab Arm Exchange During Multiple Sclerosis Treatment
Lesley J Page1, Jacqueline Lagunas-Acosta, Raphaela Heussen
1Research Department, Abreos Biosciences, LA Jolla, California.
Background:
Natalizumab, a therapeutic antibody used to treat multiple sclerosis, undergoes in vivo Fab arm exchange to form a monovalent bispecific antibody. Although highly efficacious, the immunosuppressive activity of natalizumab has been associated with JC polyomavirus-driven progressive multifocal leukoencephalopathy (PML). Development of assays that can distinguish between and quantify bivalent (unexchanged) and monovalent (exchanged) forms of natalizumab in clinical samples may be useful for optimizing extended interval dosing and reducing the risk of PML.
Methods:
In vitro natalizumab arm exchange was conducted, along with peptide mimotope and anti-idiotype surface capture chemistry, to enable the development of enzyme-linked immunosorbent assays.
Results:
An assay using a unique peptide Veritope TM was developed, which can exclusively bind to bivalent natalizumab. In combination with enzyme-linked immunosorbent assays that quantifies total natalizumab, the assay system allows quantification of both natalizumab forms.
Conclusions:
In this article, a novel assay for the quantification of unexchanged and exchanged natalizumab variants in clinical samples was developed. This assay will enable investigations into the clinical significance of the relationship of PK/PD with the monovalent-to-bivalent ratio, as it relates to the efficacy of the drug and risk of PML.
