Non-invasive, sensitive, accurate, and easy-to-manufacture IVDs will be critical to detect and monitor diseases where misfolded proteins play a significant role such as neurological illnesses like Alzheimer’s, cancers like multiple myeloma, among others.
You will learn:
- Why IsoAsp is an important biomarker for the humoral response, and neurodegeneration
- How next generation protein sequencing was leveraged to inform structural analysis of mAb and enable the development of this innovative immunoassay
- How rational design was applied to mAb from hybridoma to recombinant production
- Early discovery to method development and optimization of an immunoassay
- Why immunoassays are important tools in Alzheimer’s monitoring
There have been cases where researchers have trusted a kit, and they see a positive reaction only to, unfortunately, realize that the kit was actually detecting another protein because the kit’s antibody lot changed. Such was the case for the University of Toronto’s Diamandis team who spent half a million dollars and nearly two years due to an unreliable antibody. A certificate proving that the protein sequence of an antibody remains unchanged would have easily avoided the aforementioned mishaps.
More and more antibodies today are engineered in complex and innovative ways and then produced recombinantly from a known amino acid sequence. With recombinant expression, it is still vital to ensure that the end product, which is the protein produced by the expression system, indeed has the same exact sequence.
Leveraging cutting-edge technology is one of the ways that immunoassays can be refined into high-quality, accurate and sensitive IVDs. An emerging promising technology is Next Generation Protein Sequencing (NGPS), which exploits de novo protein sequencing to enable structural analysis of immunoreagents. Recently, Karolinska Instutet’s Zubarev Lab leveraged NGPS to design the first immunoassay to measure a specific Alzheimer’s biomarker in blood: levels of isoaspartate (IsoAsp) accumulation in human serum albumin (HSA), the most abundant protein in blood. This is the first report of a monoclonal antibody (mAb) specific to IsoAsp in HSA. Knowing the mAb’s sequence of the antigen-binding region was critical to facilitate high-quality, large-scale production of the diagnostic mAb to accurately pinpoint blood isoAsp levels via a simple, robust, and inexpensive method.