TY - JOUR

T1 - Assessment of immunogenicity and drug activity in patient sera by flow-induced dispersion analysis

AU - Pedersen, Morten E.

AU - Østergaard, Jesper

AU - Glintborg, Bente

AU - Hetland, Merete L.

AU - Jensen, Henrik

N1 - Funding Information: This work was supported by the Innovation Fund Denmark (Grant Number 9065-00009B) and the European Union, Horizon 2020, Fast Track to Innovation (Grant Number 878727). The DANBIO registry and the Danish Rheumatologic Biobank are acknowledged for supplying clinical data and serum samples. Jacob Rune Jørgensen is acknowledged for conducting the ELISA experiments. Niels Steen Krogh, Zitelab Aps, Denmark is acknowledged for DANBIO data management. Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - Biopharmaceuticals have revolutionized the treatment of many diseases such as diabetes, cancer, and autoimmune disorders. These complex entities provide unique advantages like high specificity towards their target. Unfortunately, biopharmaceuticals are also prone to elicit undesired immunogenic responses (immunogenicity), compromising treatment efficacy as well as patient safety due to severe adverse effects including life threatening conditions. Current immunogenicity assays are hampered by immobilization procedures, complicated sample pre-treatment, or rely on cell-based methods which all prevent reliable and continuous monitoring of patients. In this work, we present Flow Induced Dispersion Analysis (FIDA) for assessment of immunogenicity and drug activity in serum samples from arthritis patients receiving adalimumab. FIDA is a first principle technique for size-based characterization of biomolecules and their complexes under biologically relevant conditions. The FIDA methodology rely on an absolute and quantitative readout (hydrodynamic radius) thus reducing the need for positive and negative controls. Here, FIDA is applied for evaluating active adalimumab in serum by studying the interaction with its target tumor necrosis factor alpha (TNF-α). We report proof of principle for a quantitative approach for stratifying patients exhibiting presence of neutralizing and non-neutralizing antibodies based on their individual drug activity pattern. Further, it can be applied to any biopharmaceutical having soluble drug targets and it holds potential in a companion diagnostics setting.

AB - Biopharmaceuticals have revolutionized the treatment of many diseases such as diabetes, cancer, and autoimmune disorders. These complex entities provide unique advantages like high specificity towards their target. Unfortunately, biopharmaceuticals are also prone to elicit undesired immunogenic responses (immunogenicity), compromising treatment efficacy as well as patient safety due to severe adverse effects including life threatening conditions. Current immunogenicity assays are hampered by immobilization procedures, complicated sample pre-treatment, or rely on cell-based methods which all prevent reliable and continuous monitoring of patients. In this work, we present Flow Induced Dispersion Analysis (FIDA) for assessment of immunogenicity and drug activity in serum samples from arthritis patients receiving adalimumab. FIDA is a first principle technique for size-based characterization of biomolecules and their complexes under biologically relevant conditions. The FIDA methodology rely on an absolute and quantitative readout (hydrodynamic radius) thus reducing the need for positive and negative controls. Here, FIDA is applied for evaluating active adalimumab in serum by studying the interaction with its target tumor necrosis factor alpha (TNF-α). We report proof of principle for a quantitative approach for stratifying patients exhibiting presence of neutralizing and non-neutralizing antibodies based on their individual drug activity pattern. Further, it can be applied to any biopharmaceutical having soluble drug targets and it holds potential in a companion diagnostics setting.

U2 - 10.1038/s41598-022-08682-3

DO - 10.1038/s41598-022-08682-3

M3 - Journal article

C2 - 35304547

AN - SCOPUS:85126707483

VL - 12

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 4670

ER -