The GloBody Project
A Novel Anti-Drug Antibody Detection Platform
The administration of therapeutic monoclonal antibody to patients can lead to the occurrence of anti-drug antibodies, which can reduce the efficacy of treatment. As more antibody drugs are approved, this is a growing problem that is attracting attention from frontline clinicians. We developed a platform for the detection of IgG anti-drug antibodies for all therapeutic monoclonal antibodies.
In the ASK-Lab, synthetic genes encoding nanoluciferase polypeptides were inserted between the variable heavy and light domain encoding region of known antibody drugs to generate recombinant single-chain GloBodies, which retain the drug antibody paratopes and nanoluciferase activity. In the presence of anti-drug antibody molecules, the GloBody is bound by specific IgG in the sample. These complexes are captured on immobilised protein G and the nanoluciferase activity determined. The amount of light generated being indicative of the anti-drug 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 or by mailed dried blood spots. Moreover it is possible to tag recombinant antigens and develop assays to detect specific antibody responses