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GloBody Technology: Detecting Anti-Drug Antibody against VH/VL domains

Research output: Contribution to journalArticlepeer-review

Gauri K. Saxena, Ioannis Theocharopoulos, Nisha Thaslima Aziz, Meleri Jones, Sharmilee Gnanapavan, Gavin Giovannoni, Klaus Schmierer, James A. Garnett, David Baker, Angray S. Kang

Original languageEnglish
Article number1860
JournalScientific Reports
Volume10
Issue number1
Early online date5 Feb 2020
DOIs
Accepted/In press26 Dec 2019
E-pub ahead of print5 Feb 2020

King's Authors

Abstract

The occurrence of anti-drug antibodies following administration of therapeutic monoclonal antibody to patients is a growing problem that is attracting attention from frontline clinicians. Ideally, an initial indicative point of care test would provide guidance to seek testing approved by the regulatory authorities. Here we describe a platform for the detection of IgG anti-drug antibodies that may provide an initial screen for all therapeutic monoclonal antibodies. Synthetic genes encoding Nanoluciferase polypeptides were inserted between the variable heavy and light domain encoding region of known antibody drugs (alemtuzumab and adalimumab) to generate recombinant single chain GloBodies, which retain the drug antibody paratopes and Nanoluciferase activity. In the presence of anti-drug antibodies, the GloBody is bound by specific IgG in the sample. These complexes are captured on immobilised Protein G and the luciferase activity determined. The amount of light generated being indicative of the anti-drug IgG antibody levels in serum. It should be possible to assemble GloBody reagents for all therapeutic monoclonal antibodies and adapt the capture phase to include additional specific isotypes. The assay has the potential to be developed for use with a drop of blood allowing initial pre-screening in a point of care setting.

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